Biology & Biotechnology

Stem Cell Therapy ‘ ZIMISLECEL’ shows promise in Type-1 Diabetes

Context: ZIMISLECEL, a new allogeneic stem cell-derived islet cell therapy, has shown promise in a recent study involving people with Type-1 Diabetes.

Relevance of the Topic: Prelims: ZIMISLECEL; Type-1 DiabetesMains: Potential use cases of Stem Cell Therapy.

About Diabetes

Diabetes is a lifelong condition that causes a person's blood glucose (sugar) level to become too high. The hormone insulin (produced by the pancreas) is responsible for controlling the amount of glucose in the blood.
Type-1 Diabetes (insulin-dependent) is an autoimmune condition in which the body’s immune system mistakenly destroys insulin-making cells (islets cells) in the pancreas. It is characterised by deficient insulin production, and the person requires daily administration of insulin. For decades, managing T-1D has relied on insulin therapy alone.

ZIMISLECEL: Stem Cell-derived Islet Cell Therapy

Zimislecel is an investigational stem cell-derived islet therapy for Type-1 Diabetes.
Scientists made Zimislecel by growing islets from pluripotent stem cells in the lab. These stem cells were matured into functioning islets and infused into the liver in the patients with severe, long-standing Type-1 Diabetes.
Early trials show that these stem cell-derived islet cells began producing insulin again, improving blood sugar control and preventing dangerous lows.

Results of the Trials:

The early-stage trial aimed to assess the safety and efficacy of Zimislecel in restoring islet function in affected individuals.
- Within 90 days, all participants were producing C-peptide, a marker of insulin production, with levels more than doubling by day 365.
- Blood sugar control improved and 83% of participants treated no longer required insulin after one year.
- To prevent their bodies from rejecting the transplanted cells, they were placed on an immunosuppressive regimen.
Phase 3 trials of Zimislecel are underway with 50 participants from around the world and will be followed for five years.

The therapy is still underdevelopment and may have cost considerations and the side-effects related to life-long immunosuppression.

What are Stem Cells?

Stem cells are undifferentiated cells with the potential to develop into specialised cell types in the body. They can self-renew which makes them valuable for therapeutic applications.
Stem cell therapy utilises stem cells to promote the repair, regeneration, or replacement of damaged or diseased tissues within the body.

Types of Stem Cells:

Totipotent: Most versatile, with potential to differentiate into all different cell types of an organism and extraembryonic cells (including placenta and umbilical cord). Only found in fertilised eggs (zygote).
Pluripotent: Derived from inner cell mass of a blastocyst (an early-stage embryo). Can give rise to all different cell types in the body (except extraembryonic cells). E.g., Embryonic stem cells and induced pluripotent stem cells (genetically reprogrammed to the pluripotent state from adult cells).
Multipotent: More specialised than pluripotent stem cells and can differentiate into limited range of cell types within a specific tissue or organ. E.g., Hematopoietic stem cells (give rise to various blood cell types), mesenchymal stem cells (can differentiate into bone, cartilage, fat cell etc.)

Unipotent: Most specialised type of stem cells, can only renew themselves and differentiate into one specific cell type. E.g., Stem cells in skin that can only differentiate into another skin cell.

Also Read: HC permits Stem Cell Therapy for two kids with autism

India’s first Tribal Genome Sequencing Project

Context: Gujarat has become the first state to launch a genome sequencing initiative focused exclusively on tribal communities.

Relevance of the Topic: Prelims: Key facts about Genome, Genome Sequencing and its applications, Genome India Project; Tribal Genome Sequencing Project.

Tribal Genome Sequencing Project

The project- Creation of Reference Genome Database for Tribal Population in Gujarat- is being implemented by the Gujarat Biotechnology Research Centre.
Aim: To identify genetic health risks and improve access to personalised healthcare solutions for tribal populations.
The initiative will sequence the genomes of 2000 individuals from tribal communities in 17 districts in the State.

Significance:

Tribal populations in India face a disproportionate burden of genetic disorders like- sickle cell anaemia, thalassemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, certain forms of cancer etc. There is a longstanding gap in genomic data for India's tribal populations. The genetic database could lead to the early detection and better treatment of the inherited diseases.

What is Genome Sequencing?

A genome is an organism’s complete set of DNA. It is a collection of all the genes and the regions between the genes contained in our 23 pairs of chromosomes.
- Each chromosome is a contiguous stretch of DNA string composed of millions of individual building blocks called nucleotides or bases [adenine (A), cytosine (C), guanine (G), and thymine (T)].
- These bases (A, T, G and C) are arranged and repeated millions of times in different combinations.
Whole-genome sequencing is the decoding of the entire DNA present in the human cell, i.e., determining the precise order of the four nucleotide bases in DNA.

Applications of Genome Sequencing:

Disease Diagnosis: Identify genetic mutations and variations, evaluate rare disorders and even cancer from a genetic viewpoint.
- E.g., Nearly 10,000 diseases (including cystic fibrosis and thalassemia) are the result of a single gene malfunctioning.
- Mutation in MYBPC3 (Cardiac Myosin binding protein) leads to cardiac arrest at young age (found in 4.5% of Indian population but is rare globally).
Personalised Drug Development: Can identify genetic targets for drug development and testing, leading to the development of more effective and personalised drugs.
Prenatal Screening: Can be used as a tool for prenatal screening to investigate whether the foetus has genetic disorders/anomalies.
Forensics: Genome sequencing can be used to identify suspects in criminal investigations and to establish paternity in cases of disputed parentage.
Evolutionary Biology: Can help trace the evolutionary history of species and understand the mechanisms underlying evolution.
Agriculture: Can help identify genes that contribute to desirable traits in plants and animals, allowing for the selective breeding of crops and livestock.

Also Read: Genome Sequencing and the Genome India Project

India set to integrate Rare Blood Donor Registry with e-Rakt Kosh

Context: National Institute of Immunohaematology (NIIH), Mumbai under the India Council of Medical Research (ICMR) has launched India’s first national rare blood donor registry to support patients with rare blood types who require frequent transfusions, particularly those with thalassemia or sickle cell disease.

Relevance of the Topic: Prelims: Key facts about ICMR-Rare Donor Registry of India; E-RaktKosh

ICMR-Rare Donor Registry of India

NIIH has for the first time created a national 'rare blood donor registry' for patients with rare and uncommon blood types who need frequent transfusion especially in conditions such as thalassemia and sickle cell disease.
The portal called the ICMR-Rare Donor Registry of India (RDRI) already includes over 600 donors with rare antigen combinations and 250 very rare blood donors, including 170 Bombay blood group donors.
ICMR-NIIH is now in talks with the Director General of Health Services (DGHS) so that the rare donor registry portal can be integrated with e-Raktakosh, the Centralised Blood Bank Management System platform which provides information about blood availability.

Estimated Daily Blood Requirement in India is ~40,000 to 50,000 units per day or 15-18 million units of blood per year, but we have a shortage of 3-5 million units/year (approx. 10,000-14,000 units/day).

Need for integrating Rare Blood Donor Registry with e-Rakt Kosh

Rare blood groups occur in less than 1 in 1000 individuals, often characterised by absence of high-frequency antigens (HFA), or have a null phenotype (absence of all antigens in a group). E.g., Bombay Blood group, Rh-null (Golden blood) etc.
In the majority of blood banks in India, only ABO and RhD antigens are matched before issuing red blood cell components. However, the International Society of Blood Transfusion (ISBT) has recognised over 360 antigens across 47 blood group systems.
Blood banks do not routinely test for minor blood group antigens. As a result, a mismatch of minor antigens between donor and recipient blood group profiles can lead to red cell alloimmunisation (immune response against foreign RBC antigens after blood transfusion). This reduces the effectiveness of blood transfusions. As a result, about 25% of all immunised patients have reported unsatisfactory transfusion support.

To overcome this challenge, an inventory of extensively typed blood donors and rare blood type donors is required.

Significance:

The integration will help people with rare blood groups easily trace blood banks and procure blood.
It will also assist the blood banks manage their stock and donors through a centralised system.

Step-and-shoot spot-scanning Proton Arc Therapy for Cancer

Context: A technique called step-and-shoot spot-scanning proton arc therapy (SPArc) has been successfully used to treat a patient’s adenoid cystic carcinoma for the first time. SPArc works by targeting tumours with protons while sparing surrounding tissue.

Relevance of the Topic: Prelims: Key facts about New Emerging Technologies: Cancer Treatment.

Step-and-shoot spot-scanning Proton Arc Therapy (SPArc)

SPArc is an advanced radiation therapy that delivers precise proton beams to target tumours in sensitive areas.
The treatment includes a computer programme that scans through all possible spots and energy layers where the proton beams could be delivered.
- An energy layer is a slice of tissue that receives proton beams of a specific energy. It determines the proton beam’s range, i.e., how far it is able to penetrate the tissue.
When the machine fixes one energy level, it deposits the radiation dose in that energy layer. Then the machine switches to the next energy level and repeats the process.

Advantage:

The team compared the techniques: SFO-IMPT (standard proton therapy) and step-and-shoot SPArc.

Reduces radiation exposure: Owing to its spot-scanning and precision, the SPArc method reduced radiation delivered to the brainstem (by 10%), optical chiasm (56%), oral cavity (72%), and spinal canal (90%) over SFO-IMPT. This is particularly significant to treat cancers (tumours) of the head and neck, as it can reduce radiation exposure to sensitive areas like the brain stem and spinal cord.

Concerns: The full clinical implementation of the technology is under development. It is very expensive and is often suitable for a small patient population.

Important Cutting-Edge Technologies for Cancer Treatment:

S.No.	Technology	Details
1.	Chemotherapy	Involves administration of drugs that interfere with cell division to slow down the growth of tumours. Limitations: These drugs can disrupt the cell division of normal cells too, causing complications.
2.	Radiation Therapy	Radiation therapy directs high-energy radiation at the part of the body where a tumour is located. Limitations: The radiation process is not perfect and the nearby tissues are often harmed.
3.	Image-guided Radiation Therapy	Form of radiation therapy that uses imaging techniques to precisely locate and treat cancerous tissue. Allows for higher doses of radiation to be delivered to tumour while minimising exposure to surrounding healthy tissues.
4.	Proton Therapy	Type of radiation therapy that uses high-energy proton beams to destroy cancerous cells. Particularly useful to treat tumours located in sensitive areas (brain, eyes and spinal cord) where traditional radiation therapy can cause severe side effects.
5.	Precision Medicine	Uses genomic information (genetic profile of their tumour) to personalise treatment for cancer patients.
6.	Immunotherapy	i. CAR-T Cell Therapy (cell-based gene therapy which involves genetically modifying T-cells to help them attack cancer cells)ii. Utilising Monoclonal Antibodies iii. Injecting Cancer Vaccines

Bharat Biotech and GSK to develop Shigella Vaccine

Context: Hyderabad-based Bharat Biotech has partnered with GSK (a British multinational pharma company) for the ongoing development and potential use of the Shigella vaccine candidate, altSonflex1-2-3.

Relevance of the Topic: Prelims: Basic idea about how vaccines work; Antigens; Generalised Modules for Membrane Antigens; Shigella.

About Shigella

Shigella is a group of bacteria that causes shigellosis, a type of food poisoning.
Transmission: swallowing material contaminated by faeces, contaminated food and water.
Symptoms: stomach pain, fever, and watery or bloody diarrhoea.
Shigella has the distinction of being one of the first bacterial pathogens to be reported to be resistant to multiple antibiotics.

Shigella Vaccine

The Shigella vaccine utilises GMMA technology, a platform developed by GSK’s Global Health team. The technology employs outer membrane vesicles (OMVs) from bacteria to deliver antigens that activate the immune system.
The aim is to advance the development and potential distribution of the vaccine in low- and middle-income countries, where Shigella is a leading cause of diarrhoea among children under five.

Generalised Modules for Membrane Antigens (GMMA) Technology

GMMA is a technology platform to produce Outer Membrane Vesicles (OMV)-based vaccines.
- OMVs are naturally produced sub-units of bacterial pathogens with multiple surface-exposed antigens.
- OMVs can be used as a vehicle for delivering specific antigens of interest in therapeutic applications, such as vaccines, to induce immune response.
GMMA are OMVs derived from gram-negative bacteria modified through genetic engineering.
GMMA-based vaccines present a variety of bacterial antigens (resembling a natural bacterial infection) to the immune system. It stimulates a strong immune response, often without requiring adjuvants, and can target various bacterial diseases, such as Shigella.

Significance:

GMMA technology is low-cost and scalable, making it ideal for producing affordable vaccines for low-income countries.
It could help reduce illness and mortality rates while indirectly decreasing antibiotic use and addressing antimicrobial resistance (AMR).

Air India Plane Crash: How DNA Identification Works?

Context: After the Air India Boeing 787 Dreamliner crash in Ahmedabad, Gujarat, the authorities are using DNA analysis to identify the remains of those killed in the accident.

DNA identification is the gold standard for identifying human remains, especially after mass fatality events in which bodies might not be easy to identify otherwise.

Relevance of the Topic:Prelims: DNA Profiling: Challenges & Methods; Applications of DNA Profiling.

What is DNA Profiling?

DNA profiling is the technique used to identify individuals by analysing the unique patterns in their DNA.
With the exception of identical twins, every person has a unique DNA that is present in nearly every cell of their body.

DNA Identification: Sample Collection & Analysis

DNA samples have to be collected as soon as possible from the body. As soon as an individual dies, their DNA begins to degrade.
- Extent of degradation depends on the kind of tissue DNA is extracted from, and the conditions in which the body is kept.
- DNA from soft tissues degrades much faster than that from hard tissues (bones and teeth).
Collected samples need to be stored in a cool and dry environment. They should ideally be frozen at minus 20 degrees Celsius, or in the case of soft tissues (skin, muscles, etc.), they may be stored in 95% ethanol.
For identification of the collected DNA sample, reference samples are collected from biological relatives. Parents and children of the victim are ideal candidates for providing these samples, given that they share 50% of each others’ DNA.

Methods of DNA Analysis

After the samples are collected, the next step is to extract DNA from them. Depending on the quality of the collected DNA, scientists can choose between a number of different methods of analysis.

Short Tandem Repeat (STR) Analysis:

The method evaluates short tandem repeats, which are essentially short repeating sequences of DNA. STRs are used for DNA identification as they widely vary between individuals.
STRs are typically found on nuclear DNA which is located within the nucleus of a cell. Therefore, to carry out STR analysis it is essential that the nuclear DNA extracted from the sample is not degraded.

Mitochondrial DNA (mtDNA) Analysis:

This method is used when nuclear DNA is degraded or unavailable.
mtDNA is found in mitochondria, the cell’s energy-producing organelles. As mtDNA is present in multiple copies within the cell, it is easier to recover from human remains that are not well preserved.
mtDNA is passed down by the mother ‘unchanged’ to all her children. The samples can be matched with reference samples from their mother, maternal grandmother, siblings, maternal aunts or distant relatives from the maternal line of inheritance.

Y chromosome Analysis:

Humans have two types of sex chromosomes, X and Y: biological males typically have one X and one Y chromosome, and biological females typically have two X chromosomes.
In this method, a panel of STR on Y chromosomes, passed on from father to son, is examined to match the remains of the victim with their male relatives.
Any member of the paternal line, including brothers, paternal uncles, and paternal male cousins, may be used for matching.

Single Nucleotide Polymorphisms (SNPs) Analysis:

The method is typically used when the DNA to be analysed is highly degraded.
A SNP is a variation in the DNA sequence where a single base (A, C, G, or T) at a specific location differs among people.
Given that SNPs are unique to each person, they can be used for identification purposes with the help of reference samples taken from the victim’s personal belongings (E.g., a toothbrush and hairbrush). This method is not as effective as STR analysis.

Also Read: DNA Profling

India’s fight against rare diseases

Context: Patients suffering from rare diseases who need life-long therapy have been urging the Central government to invoke the compulsory licensing clause.

Relevance of the topic:

Prelims: National Policy for Rare Diseases, 2021.

Mains: Rare Diseases: Challenges & Interventions.

Compulsory Licensing Clause

Provision under Section 84 of the Indian Patents Act, 1970 that allows the government to grant licences to third parties to produce, use, or sell a patented invention without the consent of the patent holder.
Grounds for Compulsory Licensing:
- When the patented invention is not available to the public at a reasonable price; not being worked in India; necessary for public health.
- When the patent holder has engaged in anti-competitive practices.

TRIPS permits member countries to issue compulsory licences for certain purposes, including public health. E.g., in 2012, India granted its first compulsory licence to Natco Pharma to produce a generic version of cancer drug (Sorafenib) which was patented by Bayer.

About Rare Diseases

Rare Disease is a debilitating lifelong disease or disorder that affects a small number of people compared to the general population.
There is no universally accepted definition of rare diseases.
- WHO defines rare disease with a prevalence of 1 or less per 1000 population.
- India accepts that a disease prevalence of less than 100 patients per 100,000 people is categorised as a rare disease.

Rare Diseases in India

India accounts for one-third of the global rare disease incidence, with over 450 identified diseases. Roughly about 8 crore-10 crore Indians suffer from one rare disease or another; over 75% are children.
Moreover, 70-80% of rare diseases are genetic in nature, and thus are asymptomatic. In India, there are between 7000 – 8000 rare diseases, but less than 5% have therapies available to treat them.

Key features of National Policy for Rare Diseases, 2021:

The rare diseases have been identified and categorised into 3 groups as below:
- Group 1: can be treated by one-time curative treatment. E.g., Tyrosinemia can be treated through haematopoietic stem cell transplantation or organ transplantation.
- Group 2: require long-term or lifelong treatment with lower-cost interventions. E.g., Osteogenesis.
- Group 3: Definitive treatment exists, but is very expensive. E.g., Gaucher disease, cystic fibrosis, spinal muscular atrophy, and Duchenne muscular dystrophy.
National Consortium for R&D on Therapeutics for Rare Diseases is established for streamlining the research activities for rare diseases.
Financial support of up to Rs. 50 lakhs per patient is provided for the treatment at the notified Centres of Excellence (CoEs) for Rare Diseases. As of 2024, 63 rare diseases are included under the Policy.
To receive financial assistance for treatment of rare disease, the patient can approach any Centre of Excellence to get registered.

Challenges:

Lack of proper definition: ‘Rare diseases’ are not precisely defined due to a lack of sufficient data and epidemiological assessments.
Issues in Diagnosis and low diagnostic accuracy: For rare disease patients, it takes an average of seven years for their conditions to be diagnosed (if at all).
Limited facilities for treatment: Less than 50% of the 450-odd rare diseases identified in India are treatable. Treatments approved by the Drugs Controller General of India can be availed only from Centres of Excellence (CoEs). Since CoEs are few (12), unevenly distributed, and uncoordinated, it results in late diagnosis and lack of timely availability of treatment.
Lack of funds: The Budget’s allocation for rare diseases, although increasing over the years, remains low. Cap of ₹50 lakh on Group 3 rare diseases forces patients to abandon the treatment or rely on crowd-funding initiatives.

Interventions related to Rare Diseases:

Exemption from Goods & Services Tax (GST) and Basic Customs Duty on drugs imported for Rare Diseases for individual use and through the Centre of Excellence.
Production Linked Incentive Scheme 2.0 for Pharmaceuticals, with an outlay of INR 15000 Crore providing financial stimulus to orphan drugs development under Category 1 of pharmaceutical goods in the Production Linked Incentive (PLI) Scheme.
Central Drugs Standard Control Organisation (CDSCO) has made provisions for fast-track processing of applications for rare diseases drugs for drug trials and experimental therapies.
Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN), a non-profit clinical genomics research network, has established a network of clinicians and scientists for the largest clinical genomics research networks in India.
Council of Scientific & Industrial Research has established an Indian Genetic Disease Database to keep track of mutations in the genes responsible for genetic diseases in India.

Way Forward

The central government must frame a standard definition of rare diseases, increase budgetary outlays, funding for drug development and increase the number of CoEs.
The government must incentivise domestic drug manufacturers under PLI, reduce clinical trial requirements in appropriate cases, and explore options such as repurposed drugs, bulk-import, and increase the availability of generic drugs.
State governments must introduce social assistance programmes and develop satellite centres under the CoEs.

Using Bacteriophages to combat Antimicrobial Resistance

Context: Scientists are considering the therapeutic use of bacteriophages to kill bacteria, as an alternative to Antibiotics. Pharmaceutical companies are losing interest in developing new antibiotics due to increasing Antimicrobial Resistance.

Relevance of the Topic: Prelims: Key facts about Antimicrobial Resistance (AMR); Bacteriophages.

What is Antimicrobial Resistance (AMR)?

Resistance acquired by any microorganism (bacteria, viruses, fungi, parasite, etc.) against antimicrobial drugs (such as antibiotics, antifungals, antivirals, antimalarials) that are used to treat infections.
Microorganisms that develop AMR are referred to as superbugs. Due to AMR, standard treatments become ineffective, infections persist and may spread to others.
WHO has identified AMR as one of the top threats to public health. Estimated 5 million deaths globally are related to AMR every year. This is expected to double by 2050.

Largely, pharmaceutical companies have lost interest in developing new antibiotics. Scientists are considering the use of Bacteriophages as an alternative (or complementary) to Antibiotics.

About Bacteriophages

Bacteriophages are ‘good viruses’ that naturally prey on bacteria.
They are ubiquitous, i.e., present in the water, in the soil, in our gut, on skin, etc.
There are believed to be 10-times as many phages as bacteria on the earth.

Therapeutic uses of Bacteriophages:

Phages have been used for burns, foot ulcers, gut infections, respiratory infections, urinary tract infections, etc. There are two main strategies that have been used.

Natural Phage Therapy: Bacteria are isolated from the infected tissue. Labs identify which phage works against the particular bacteria. The selected phage (from phage bank) is cultured and administered into the patient.
Genetically engineered phages: Modified in the lab to target a broader range of bacterial strains.

Challenges in therapeutic uses of Bacteriophages:

Narrow Range: Unlike an antibiotic, which may be able to kill many species of bacteria, phages may only kill a few strains of a particular bacterium. This is because phages are very specific to bacteria. So, it is challenging to conduct randomised controlled trials when the drug needed for each patient may be different.
Regulatory Issues: Bacteria can evolve to be resistant to a phage. However, the phages can also evolve to avoid the bacterial resistance. The drug is not a constant but an evolving entity. This poses problems in regulatory clearance.

Researchers are currently working to create a device in which all of the following steps can be conducted: isolate the bacteria from an infection, sequence its genome, use AI to determine which phage genome is the most likely to work, create the phage from scratch in the device, and administer it to the patient on the spot.

Thermophile Bacteria

Context: Researchers have discovered thermophilic bacteria capable of producing antimicrobial compounds, particularly from the Actinobacteria group in the Rajgir hot spring in Bihar.

Relevance of the Topic: Prelims: Key facts of Thermophiles bacteria.

Thermophilic Bacteria

Thermophiles are heat-loving bacteria that can survive in extreme temperatures ranging from 45°C to 70°C. They thrive in hot springs, deep-sea vents, and compost piles, etc.
To compete with other microbes, some thermophiles produce strong antibiotics. These antibiotics kill or suppress other bacteria, helping thermophiles survive better.

Findings from Rajgir Hot Spring Study:

Using a method called 16S rRNA metagenomics, researchers identified one major group of bacteria- Actinobacteria.
Actinobacteria constituted 40-43% of the microbial diversity in the lake, a much higher share than typically observed in hot springs (generally ~20%).
This group of bacteria is well-known for producing antibiotics like streptomycin, tetracycline, and erythromycin. However, not all thermophiles can produce antibiotics.
Seven strains of Actinobacteria were found that produced potent antimicrobial compounds. These antimicrobial compounds are capable of inhibiting the growth of several pathogenic bacteria, including E. coli, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.
Researchers have succeeded in isolating a compound called diethyl phthalate from Actinomycetales bacteria found in the hot spring. Using gas chromatography-mass spectrometry (GC-MS), they identified its antibacterial activity against Listeria monocytogenes, a serious foodborne pathogen. This finding highlights the potential use-case of hot spring microbes.

Significance of Thermophiles:

Produce antibiotics: Discovering antibiotic-producing thermophiles offers a promising solution to combat antimicrobial resistance, which could add $1 trillion to global healthcare costs by 2050.
Produce enzymes for diagnostics: Enzymes from thermophiles like Thermus aquaticus are used in PCR testing, which became a backbone of COVID-19 diagnostics.
Heat-resistant enzymes from thermophiles are used in biotechnology, molecular biology, and chemical industries.
Biofertilisers: A 2018 study by Banaras Hindu University found that thermophiles from Chumathang hot spring in Leh enhanced plant growth, suggesting application in biofertilisers and heat-stress resistant crops.

Why Covid cases are rising?

Context: The number of COVID-19 cases in India has been steadily increasing with Maharashtra, Karnataka, Tamil Nadu, and Kerala accounting for the majority of new infections. A new virus subvariant- NB.1.8.1 was found in a sample and sent to India's genome sequencing consortium.

Relevance of the Topic:Prelims: Key facts about SARS-CoV-2 Virus.

SARS-CoV-2 Virus

Coronavirus (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

SARS-CoV-2 is a novel beta coronavirus belonging to the same subgenus as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
Coronaviruses are positive-stranded RNA viruses with a crown-like appearance due to the presence of spike glycoproteins on the envelope.
Like other RNA viruses, SARS-CoV-2 is prone to genetic evolution/mutation over time. This results in mutant variants that may have different characteristics than its ancestral strains.
Origin: widely postulated to have originated from an animal, implicating zoonotic transmission.
Transmission: Exposure to respiratory droplets carrying the infectious virus from close contact or droplet transmission from presymptomatic, asymptomatic, or symptomatic individuals.
Vaccines: mRNA vaccines (Pfizer); viral vector vaccines (Covishield; Sputnik V); inactivated viral vaccines (Covaxin); DNA vaccines (ZyCov-D); protein subunit vaccines (Novavax).

SARS-CoV-2 has not disappeared. It has become part of a recurring cycle of illnesses, similar to the flu. Periodic waves of Covid-19, like other endemic respiratory diseases, are expected throughout the year.

Several factors could be contributing to the rise in cases:

Waning immunity: Protection from vaccination or past infection decreases with time, leaving individuals more vulnerable to reinfection.
New variants: Like other viruses, SARS-CoV-2 continues to mutate. Some of these new variants may spread more easily or evade immunity to a greater extent.
Seasonal patterns: Respiratory viruses often spread more efficiently in colder or more humid periods.
Not enough testing: Covid-19 is now considered endemic, and testing and genome sequencing efforts have been scaled back, delaying the identification of outbreaks.
High-risk groups: Individuals with weakened immune systems or severe comorbidites remain especially vulnerable.

India's first gene-edited Sheep

Context: A university in Kashmir (SKUAST-Kashmir) has created India’s first gene-edited sheep. It is the nation’s first success in editing the genes of livestock and a major milestone in India’s push for innovation in animal biotechnology.

Relevance of the Topic: Prelims: Key concepts- gene editing, gene modification & their applications.

Gene-edited Sheep:

The lamb’s DNA was carefully altered using CRISPR-Cas9 technology. A particular gene- myostatin gene (natural brake on muscle growth) in Indian sheep was edited.
By altering this gene, researchers were able to increase muscle mass by 30%. Such a feature exists naturally only in some European breeds like the Texel, not in Indian sheep.

How is Gene Editing different?

Gene editing is distinct from crossbreeding and gene modification.

Gene editing involves using technologies like CRISPR-Cas9 which enable the addition, removal, or alteration of genetic material at specific locations within an organism’s genome. Unlike genetic modification no foreign DNA is introduced. It offers faster and safer results and aligns with India's current biotech regulations.
Crossbreeding is the traditional breeding of two different breeds from the same species to create a new breed. Generally, breeds chosen have complementary traits that will enhance the offsprings’ economic value. However crossbreeding is a slow process, with viable traits visible after a few generations.
Gene modification (transgenic animals) involves inserting news from one species into the other to create a transgenic organism.

Significance:

The progress is a turning point in livestock genetics. Gene editing allows precise changes without foreign genes which makes it more acceptable for regulators and consumers alike. This can have applications in:

Production of gene-edited species (increased muscle mass) for meat consumption.
Increasing output in cattle (E.g., Milk, wool etc.)
Elimination of disease causing genes in cattle (disease-resistant animals).

What is Anaemia?

Context: 57% of women in their reproductive age in India have undiagnosed and untreated Anaemia. This increases the risk of pre-term birth, low birth weight, and life-threatening maternal complications which contribute to maternal and perinatal morbidity and mortality.

Relevance of the Topic:Prelims: Key facts about Anaemia.

About Anaemia

Anaemia is a condition in which the number of red blood cells (RBCs), and consequently their oxygen-carrying capacity, is insufficient to meet the body’s physiological needs.
Anaemia impairs the body’s ability for gas exchange by decreasing the number of RBCs transporting oxygen and carbon dioxide.
- The function of the RBCs is to deliver oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs.
- This is accomplished by using haemoglobin (Hb), a protein composed of haem and globin.
Symptoms: Fatigue, weakness, dizziness and shortness of breath etc.
Treatment: Anaemia is preventable and treatable. Treatments include folic acid supplements, iron chelation, and blood transfusions and bone marrow transplants (in advanced cases).

Factors causing Anaemia

Anaemia results from one or more of the following process:

Iron deficiency is the most common cause of anaemia globally (around 50% cases).
- Iron is necessary for synthesis of haemoglobin (Hb).
Other nutritional deficiencies (including folate, vitamin B12 and vitamin A)
Defective red cell production, increased red cell destruction or blood loss.
- Inherited or acquired disorders that affect Hb synthesis, red blood cell production or red blood cell survival can all cause anaemia.
Acute and chronic inflammation, helminths infestation (hookworm, flukes), parasitic infections (like Malaria).

Impacts

Iron deficiency anaemia results in impaired cognitive and motor development in children and decreased work capacity in adults.
In pregnancy iron deficiency anaemia can lead to perinatal loss (miscarriage, still birth), prematurity and low birth weight babies.
Iron deficiency anaemia adversely affects the body’s immune response.

Burden of Anaemia in India

India’s anaemia burden has grown alarmingly with NFHS-5 (2019-21) finding that:
- 57% of women in the age group (15-49)
- 67% of children between 6-59 months
- 59% in adolescent girls (15-19 yrs)
- 31% in adolescent boys (15-19 yrs)
This is a rise from the data in NFHS-4 (2015-16).

Government Initiatives to tackle Anaemia burden

1. Anaemia Mukt Bharat strategy (2018):

6X6X6 strategy to reduce prevalence of anaemia in children, adolescents, and women.

Reduce Anaemia among six beneficiary age groups:
- children 6-59 months
- children 5-9 years
- adolescents 10-19 years
- women of reproductive age (15-49 years)
- pregnant women
- lactating women
Implementation of six interventions:
- Prophylactic Iron Folic Acid Supplementation
- Periodic deworming (Albendazole tablet)
- Intensified year-round Behaviour Change Communication Campaign
- Testing of anemia using digital invasive haemoglobinometer
- Point of care treatment
- Mandatory provision of Iron Folic Acid fortified foods in public health programmes
Addressing non-nutritional causes of anemia in endemic pockets, via six institutional mechanisms.

2. Mission Poshan 2.0:

Supplementary nutrition is provided to children (6 months to 6 years), pregnant women, lactating mothers and Adolescent Girls (14 to 18 years in Aspirational districts and North-East States).
Poshan Maahs and Poshan Pakhwadas: Celebrated in September and March-April, dedicated activities for awareness on anaemia are conducted.

3. Rice Fortification Initiative:

Government is supplying fortified rice enriched with iron, folic acid and vitamin B12 under the Targeted Public Distribution System (TPDS), Pradhan Mantri Poshan Shakti Nirman (PM-POSHAN) Scheme, Integrated Child Development Services (ICDS) Scheme in all States and Union Territories.

4. Diet and Biomarkers Survey in India (DABS-I) survey (2022):

New survey launched to map diet, nutrition and health status pan India. It will collect individual dietary intake data of different age groups for correct estimates of anaemia among urban and rural populations.

5. AnemiaPhone:

It is a latest technology to accurately, quickly, and cheaply assess iron deficiency, recently transferred to the Indian Council of Medical Research.
It requires a small finger prick, a drop of blood is placed on a test strip, and the device can determine iron deficiency in a few minutes. It would enable access to rapid screening, and diagnosis of iron deficiency at the point of need.