CRISPR-Cas9 - Gene Editing

Part of: GS-III- S&T (PT-MAINS-PERSONALITY TEST)

Background

A Chinese researcher recently claimed that he had altered the genes of a human embryo that eventually resulted in the birth of twin girls. The genes were claimed to be “edited” to ensure that they do not get infected with HIV, the virus that causes AIDS. If proven, it would be the first instance of human offspring having been produced with specific desired attributes, using newly-developed tools of gene “editing”.

What are Genes and what is gene- editing?

Genes contain the bio-information that defines any individual. Physical attributes like height, skin or hair colour, more subtle features and even behavioural traits can be attributed to information encoded in the genetic material.

An ability to alter this information gives scientists the power to control some of these features. Gene “editing” — sometimes expressed in related, but not always equivalent, terms like genetic modification, genetic manipulation or genetic engineering — is not new.

What is CRISPR-Cas9?

The clustered, regularly interspaced, short palindromic repeats, or CRISPR/CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system has revolutionised genetic manipulations and made gene editing simpler, faster and easily accessible to most laboratories.

CRISPR technology is basically a gene-editing technology that can be used for the purpose of altering genetic expression or changing the genome of an organism.

• The technology can be used for targeting specific stretches of an entire genetic code or editing the DNA at particular locations.
• CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function.
• Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops. However, its promise also raises ethical concerns.

How it works?

CRISPR-Cas9 technology behaves like a cut-and-paste mechanism on DNA strands that contain genetic information.

• The specific location of the genetic codes that need to be changed, or “edited”, is identified on the DNA strand, and then, using the Cas9 protein, which acts like a pair of scissors, that location is cut off from the strand. A DNA strand, when broken, has a natural tendency to repair itself.
• Scientists intervene during this auto-repair process, supplying the desired sequence of genetic codes that binds itself with the broken DNA strand.

Concerns: Tampering with the genetic code in human beings is more contentious. Leading scientists in the field have for long been calling for a “global pause” on clinical applications of the technology in human beings, until internationally accepted protocols are developed.

Issues:

Study by Stanford University, U.S., found that the CRISPR-Cas9 system introduces unexpected off-target (outside of the intended editing sites) effects in mice. The fear that the CRISPR system is being prematurely rushed for clinical use lingers. Three recent reports have exacerbated this fear even further.

• Studies highlighted that CRISPR-Cas9-edited cells might trigger cancer.
• May increase the risk of mutations elsewhere in the genome in those cells.
• Although, CRISPR-Cas9 technology has been successfully used to cure several diseases however, it remains many things are not clear like how we should determine which disease or traits are appropriate for gene editing.
• Ethical concerns: In addition, there are concerns with manipulating human embryos for own interest.

Conclusion: This CRISPR technology is indeed a path-breaking technology, to alter genes in order to tackle a number of conventional and unconventional problems, especially in the health sector. However, experiments and tests to validate its use must be subjected to appropriate scrutiny by the regulators, and their use must be controlled to prevent commercial misuse.

INDIGEN PROJECT

Part of: GS-III- S&T (PT-MAINS-PERSONALITY TEST)

What is Gene Sequencing?

A genome is the DNA or sequence of genes in a cell. Most of the DNA is in the nucleus and intricately coiled into a structure called the chromosome.

Every human cell contains a pair of chromosomes, each of which has three billion base pairs or one of four molecules that pair in precise ways. The order of base pairs and varying lengths of these sequences constitute the “genes”.

Sequencing a genome means deciphering the exact order of base pairs in an individual. It has been known that the portion of the genes responsible for making proteins called the exome occupies about 1% of the actual gene. The genome has to be mapped in its entirety to know which genes of a person’s DNA are “mutated”.

Gene Sequencing projects across world:

• The UK was the first to launch a program called Genomics England which aims to sequence up to 100,000 whole genomes from patients with rare diseases, their families, and cancer patients.
• Australia is working on the 4-year 100,000 Genomes Project, sequencing patients with rare diseases and cancer to create a massive database for R&D.
• Estonian Genome Project Foundation collected data from 52,000 adult donors by February 2014 and in March, 2019 has offered a further 100,000 people free genetic testing.
• In the USA, the Precision Medicine Initiative (PMI), with its 1-million-volunteer health study, is gathering a large database of health data including genetics and lifestyle factors. The Mayo Clinic (American non-profit academic medical center) will analyze and store one million blood and DNA samples.
• In 2016, France announced the “France Médecine Génomique 2025” program, aiming to open 12 sequencing centers and ensure 235,000 whole genome sequencing (WGS) a year which can be used as diagnostics tool.
• The non-profit consortium GenomeAsia 100K decided to generate genomic data for Asian populations. Supporters of the initiative include genomics companies Macrogen in Korea and MedGenome in India, as well as Illumina.
• The Qatar Genome Program aims to establish the Qatari Reference Genome Map by sequencing 3,000 whole genomes, which accounts for around 1% of the Qatari population.
• In 2010, the BGI genomics institute in Shenzhen, China hosted a higher sequencing program which aims at sequencing one million human genomes and will include subgroups of 50,000 people, each with specific conditions such as cancer or metabolic disease.

India’s Indigen project and other projects:

• The CSIR project is part of a programme called “IndiGen”.
• Though CSIR first sequenced an Indian genome in 2009, only now it has been able to scale up whole-genome sequencing and offer them to the public.
• The driving motive of the project is to understand the extent of genetic variation in Indians, and learn why some genes linked to certain diseases based on publications in international literature does not always translate into disease.
• Under “IndiGen”, the CSIR drafted about 1,000 youth from a pool of about 5,000 and included representatives from every State and diverse ethnicities.
• Every person whose genomes are sequenced would be given a report.
• The participants would be informed if they carry gene variants that make them less responsive to certain classes of medicines.
• The project involved the Hyderabad-based Centre for Cellular and Molecular Biology (CCMB), the CSIR-Institute of Genomics and Integrative Biology (IGIB).
• The project ties in with a much larger programme Genome India project,

Genome India project:

• It is funded by the Department of Biotechnology (DBT) to sequence at least 10,000 Indian genomes.
• 22 partner organisations including public health institutions will be roped in that have obtained regulatory ethical clearances.
• Investigators in hospitals will lead the data collection through a simple blood test from participants and the information will be added to bio banks.

• The project will aim to make predictive diagnostic markers available for some priority diseases such as cancer and other rare and genetic disorders.
• The department has also initiated an outreach programme to provide genetic diagnosis and counselling to families affected by common genetic disorders in certain districts.

Medgenome project:

• Sequoia-backed MedGenome, a start-up is planning to fund its own research in the area of DNA sequencing and precision medicine, with an aim to licence the findings to biotechnology firms and drug makers.
• Launched in 2013, San Francisco- and Bengaluru-based MedGenome Labs Pvt. Ltd has a network of Next Generation Sequencing (NGS) laboratories in India, Singapore and the US.
• Its research is in four main areas: cancer immunotherapy, inherited diseases, diabetes and ophthalmology.
• About 70% of the company’s revenue is earned from project-based research mainly for US-based pharmaceutical clients, while the rest is from consumer diagnostic tests in Asia.
• Its labs combine state-of-the-art testing equipments and powerful computers to perform DNA sequencing that is used for a wide variety of purposes such as biomarker discovery, drug research and new market discovery.

Prospects of gene Sequencing:

• Determining unique genetic traits, susceptibility and resilience to diseases.
• For new advancements in medical science like predictive diagnosis and precision medicine, genomic information is the backbone.
• The technique has allowed drug makers to come up with medicines that work on a select group of individuals based on similar genetic makeup, as against generic drugs used with little success so far.
• With the help of DNA sequencing, healthcare practitioners are using the new technique called cancer immunotherapy to treat cancer where the patient’s genes are altered to help his or her immune system fight cancer cells.
• The common early onset disorders with “complex” inheritance like asthma, type-1 diabetes mellitus, and the epilepsies and behavioural phenotypes of autism and attention deficit hyperactivity disorder can be understood.

Issues with gene sequencing:

• Synthetic human genome could be created which will be against the law of nature.
• Morality of eugenics, which is the theory and practice of improving the genetic quality of the human population.
• Danger of genetic misuse.
• Biosafety and biosecurity concerns related to implications of technology.
• Selection of genes for specific traits might change the dynamics of genes and alter the ecological balance.
• Agencies that fund large genomic initiatives have tended to treat the data these projects produce as a community resource to be made publicly available before thorough analysis by the consortia that generate them which violates privacy.
• The inability to anticipate the types of benefits and risks associated with future research using donated biological materials raises major ethical worries.
• By its very nature, a fully or partially sequenced individual genome can reveal information about genetically based or -contributed characteristics that is unknown to the participant.
• Where targeted populations comprise organized cultural entities like different tribes consultation demonstrates respect for the moral authority of those communities. Community consultation or engagement, however, should not be mistaken for community consent nor does every medical-sequencing project or every population warrant advance consultation.

Rotavac

Bharat Biotech’s diarrhea vaccine ROTAVAC gets WHO pre-qualification. The WHO pre-qualification paves the way for health and humanitarian organizations such as UNICEF to procure it for public health vaccination programs across the world. Rotavirus is the most common cause of severe diarrhea and kills more than 200,000 children every year. ROTAVC is also included in the Universal Immunization Program

Sea Turtles in India

There are five species of sea turtles in Indian waters — Leatherback, Loggerhead, Hawksbill, Green and Olive Ridley.

IUCN Status of these turtles are

• Hawksbill- Critically endangered
• Green turtle- Endangered
• Leatherback- Vulnerable
• Loggerhead- Vulnerable
• Olive Ridley- Vulnerable

Mostly these turtles are found on the eastern coast of the Country. Often turtles are confused with tortoises. The major difference between the tortoise and sea turtles is that tortoises dwell on land, while turtles live in the water for some or nearly all of the time.

Mount Mayon

• It is an active stratovolcano in the Philippines region

• Stratovolcano , also known as a composite volcano, is a conical volcano built up by many layers of hardened lava, tephra, pumice, and volcanic ash
• The volcano is the centrepiece of the ALBAY biosphere reserve and Natural Park on its own.
• Mount Mayon lies in the Pacific ring of fire region, a major area in the basin of the Pacific Ocean where a large number of earthquakes and volcanic eruptions occur

Mission Innovation

The initiative was launched in the Cop21 UNFCCC in 2015. India is a member nation of the global initiative

The objectives of the initiative are,

• To accelerate public and private clean energy innovation
• To address climate change,
• Make clean energy affordable to consumers, and
• Create green jobs and commercial opportunities

It will help in achieving India’s INDC of increasing the share of clean and renewable energy in the energy basket

National Institutional Ranking Framework

The National Institutional Ranking Framework (NIRF) was approved by the MHRD and launched in 2015. This framework outlines a methodology to rank institutions across the country.

The methodology involves various parameters for ranking universities and institutions such as

• Teaching, Learning and Resources.
• Research and Professional Practices.
• Graduation Outcomes.
• Outreach and Inclusivity.
• Perception.

Assumption Island - Seychelles

Assumption Island is one of the 115 islands constituting the Seychelles archipelago. India signed a pact to develop Assumption Island, during PM Modi’s visit to Seychelles in 2015.

• Ironing out the earlier differences, India has now signed a revised agreement with Seychelles.
• Assumption Island is leased to India for the operation of a naval base and air strip by the Indian navy.
• The agreement will enable India to help Seychelles build military infrastructure for the Seychelles People’s Defence Forces.
• Seychelles has said it would “suspend” the use of military facilities on Assumption Island in case India is at war. This is because it is not a military base.
• Also, other “international partners” can also use the facilities being developed by India on the island. It is being financed entirely by India, but Seychelles retains full ownership of the facilities and sovereign rights over the island.

Human Papilloma Virus (HPV)

The National Technical Advisory Group on Immunization (NTAGI) has recommended the introduction of the HPV vaccine in the UIP. NTAGI is an advisory body that recommends vaccines for India’s Universal Immunization Programme (UIP).

Human Papilloma Virus (HPV) is a group of more than 150 viruses. It is usually harmless and goes away by itself. However, some types cause papilloma or warts in parts of the body. HPV spreads by skin-to-skin contact and is the most common sexually transmitted infection.

HPV is commonly associated with cervical cancer. India has one of the world’s highest burdens of HPV-related cancer and around 67,000 women die from this disease each year. HPV vaccines offered by private firms face clinical trial issues in India on concerns of side effects; Supreme Court is yet to decide.

Objectionable Content

The Ministry of Electronics and IT has highlighted that around 1300 social media URLs were blocked or removed in the last year. These were based on the recommendation of a government committee to deal with “objectionable content”.

The Information Technology (IT) Act 2000 and the Indian Penal Code provide for dealing with “objectionable content” posted online. Blocking is a sovereign power that is given to the government by virtue of Section 69A of the IT Act. There are concerns with the parameters for deciding a particular content is 'inappropriate' or 'objectionable'.

Pulse Polio Immunisation (PPI) - IMMUNISATION PROGRAMME

As part of the National Immunisation Day observed on 28 January, PPI programme for 2018 was launched. More than 17 crore children of less than 5 years across the country will be given polio drops.

The polio virus causes paralysis, known as acute flaccid paralysis (AFP). This is characterised by sudden muscle weakness and fever in one or more limbs. India reported its last polio case in 2011 and is also declared polio-free by WHO in 2014.

However, the immunisation drive continues as poliovirus is still circulating in other parts of the world. The injectable Inactivated Polio Vaccine (IPV) has also been introduced recently into the Universal Immunisation Programme. IPV is an injectable form of polio vaccine administered alone or in combination with other vaccines including the OPV (oral polio vaccine).

Universal Immunization Programme

Universal Immunization Programme was launched in 1985. Now mission INDRADHNUSH

The program now consists of vaccination for 12 diseases:

1. tuberculosis
2. diphtheria
3. pertussis (whooping cough)
4. tetanus
5. poliomyelitis
6. measles
7. Hepatitis B
8. diarrhoea
9. Japanese Encephalitis
10. Rubella
11. Pneumonia( Haemophilus Influenza Type B)
12. Pneumococcal diseases (Pneumococcal Pneumonia and Meningitis)

The Indradhanush mission, launched in 2014, is to fast-track the universal immunization programme. The mission aims at increasing immunisation coverage to 90% by 2018.

Prompt Corrective Action (PCA)

Union Finance Ministry as a part of the reforming process about to initiate a performance review for public sector banks. These reforms will be under the RBI’s Prompt Corrective Action (PCA). The PCA is invoked when certain risk thresholds are breached, there are three risk thresholds which are based on

• Asset quality.
• Profitability.
• Capital and the like.

The third threshold is the maximum tolerance limit, which has set NPA at over 12% and a negative return on assets for four consecutive years. Under PCA there are two types of sanctions restrictions on dividends, branch expansion and directors' compensation are of the mandatory type and curbs on lending and deposit are discretionary type.