Biology & Biotechnology

Why do we lose Muscle Mass with Age?

Context: Researchers have found out that mutations in Mitochondria result in gradual decline in mitochondrial functions which leads to the death of muscle cells. The death of muscle cells in turn leads to loss of muscle mass.

Relevance of the Topic: Prelims: Key facts about Mitochondria and Age-related muscle loss.

What is Sarcopenia?

Age-related muscle loss, called sarcopenia, is a natural part of aging.
After age 30, humans begin to lose muscle mass as much as 3% to 5% per decade.
Less muscle means greater weakness and less mobility, both of which may increase your risk of falls and fractures.

What are Mitochondria?

Mitochondria are cellular organelles found in the cytoplasm. They are called powerhouse of the cell as they generate most of the cell's energy currency- ATP (adenosine triphosphate).
Some DNA is also present in the mitochondria (mtDNA). mtDNA codes for a small number of genes, essential for the proper functioning of mitochondria.
Mitochondria are the descendants of free-living bacteria that our early single-celled ancestors then absorbed. Today, mitochondria can not survive independently of their host cell.
Inheritance: mtDNA is inherited almost exclusively from the mother. (Nuclear DNA comes from both parents)
Mitochondrial DNA is more prone to mutations compared to nuclear DNA as it is exposed to free radicals generated during energy production, which can damage DNA.
When mitochondria are impaired they do not produce sufficient energy. It causes inherited conditions like heart problems, liver failure, brain disorders, blindness and muscular dystrophy. There is no cure for mitochondrial DNA diseases at present.

Mitochondria and Age-related Muscle Loss

mtDNA molecules can suffer from age-related deletion mutations. (A deletion mutation is when one to few thousands of base-pairs become deleted from a gene)
- The deletion mutations accumulate in the mitochondrial genome (mtDNA) and can affect the expression of normal mtDNA.
- Over time, this leads to critical shortage of functional mitochondria (those producing ATP) in the muscle cells.
- If the number of functioning mitochondria becomes too low, the muscle cell is unable to properly contract and dies. This underlies the loss of muscle mass.
Significance: mtDNA deletion mutations are a useful predictor of biological age. A better understanding of the process that causes deletion mutations can help researchers develop new ways to delay age-related decline in mtDNA quality.

AIIMS devises new Breast Cancer Detection Tool

Context: The All India Institute of Medical Science (AIIMS) in New Delhi has recently unveiled an AI-based solution to assist in the early detection of Breast Cancer.

Relevance of The Topic: Prelims: Key facts about Breast Cancer; New AI Cancer Detection Tool

What is Breast Cancer?

Breast cancer results from abnormal growth in breast cells which form tumours.
- Breast cancer cells begin inside the milk ducts and/or the milk-producing lobules of the breast. The cells can spread into nearby breast tissue and create tumours.
- The earliest form (in situ) is not life-threatening if detected in early stages.
- In later cases, invasive cancers can spread to nearby lymph nodes or other organs (metastasize). Metastasis can be life-threatening and fatal.
Females at highest risk: Approximately 99% of breast cancers occur in women and 0.5–1% of breast cancers occur in men.
Treatment: Chemotherapy, radiation therapy, surgical removal of breasts etc.
Prevalence in India: Breast Cancer is the most common cancer in women in India. India ranks highest in the number of estimated breast cancer deaths (98,337) for the year 2022 among females.

Risk Factors:

Certain factors increase the risk of breast cancer, they include-

Increasing age (females over 40 years).
Lifestyle factors: Obesity, harmful use of alcohol, tobacco use, history of radiation exposure etc.
Genetic factors: The risks of developing breast cancer are markedly increased in people who inherit mutated BRCA1 or BRCA2 genes.
- BRCA1 or BRCA2 are tumour suppressor genes present in both males and females. They produce proteins that repair DNA and are responsible for the stability of genetic material.
- Mutations in these genes increase the chances of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.

About New AI Cancer Detection Tool:

The All India Institute Of Medical Science (AIIMS) in New Delhi has recently unveiled an AI-based solution that assists with the early detection of Breast Cancer.
Aim: Improving early breast cancer detection and reducing mortality by identifying breast cancer patterns specific to Indian women.
The project is part of the Indian government’s flagship scheme to establish three Centres of Excellence (CoE) in AI, focusing on healthcare, agriculture, and sustainable cities.

How will the AI model work?

The AI model will first scan a five-year database of women tested for breast cancer at some medical institutions (presently pilot study- AIIMS Delhi, NCI Jhajjar and PGI Chandigarh) regardless if they were tested negative or had developed cancer.
For identifying Indian risk factors for breast cancer, ASHA workers will collect data (after detailed conversations with families about their personal health status and family history of diseases) which will be fed into the AI tool.
After analysing the data, the AI tool will predict the risk of developing breast cancer by combining a patient’s general test results with their lifestyle and family history data.
- It will extract common risk factors and then recommend mammograms (specialised X-rays to check for signs of breast cancer) for women it thinks are cancer-prone.
- It will also help codify what constitutes a no-risk category.

Benefits of AI Cancer detection Tool:

Facilitate early screening: AI-trained systems can recognise complex features in mammograms that indicate cancer, thus picking up even the smallest signs.
Data-profiling based on risk factors: AI can interpret the data pool and identify which women may need mammograms while reassuring others with low-risk profiles.
Reduce cost: The AI-trained systems would not require a radiologist, help reduce the amount of manual work involved in screening which can lower costs.
Facilitate cancer detection in remote areas: The tool can provide advanced breast cancer screening, even in remote areas where there is a shortage of trained radiologists.

Presently, a pilot project has been initiated. If the AI tool is found to be effective, then an economic assessment will be conducted on the cost required to scale this up pan-India and take it up for licensing.

Idiopathic Pulmonary Fibrosis

Context: Recently, renowned musician Ustad Zakir Hussain passed away following complications with idiopathic pulmonary fibrosis.

Relevance of the Topic: Prelims: Key facts about Idiopathic Pulmonary Fibrosis.

What is Idiopathic Pulmonary Fibrosis?

It is a chronic, progressive lung disease characterised by scarring (fibrosis) of the lung tissue, leading to irreversible loss of lung function. The exact cause of IPF is unknown, so it is termed idiopathic.
In case of a healthy lung, the oxygen easily passes through the walls of the air sacs (alveoli) and goes into the capillaries, and eventually the bloodstream. In IPF, the fibrosis thickens and stiffens the lungs, reducing their ability to expand and take in oxygen.
- IPF specifically targets the interstitium (the tissue surrounding the air sacs). As a result, the alveoli walls get thicker, which makes it difficult for the oxygen to move into the bloodstream.
- Over time, this leads to persistent breathlessness, fatigue, and reduced quality of life.
Symptoms: Shortness of breath, prolonged dry cough, pain in joints and muscles, fatigue and weight loss.

What are the risk factors for IPF?

The exact cause of IPF is unknown, however, there are several factors that come into the play when considering the risk an individual is under to get IPF:

Age: Older people (over age 50, generally 60-70) are at a higher risk of developing idiopathic pulmonary fibrosis.
Lifestyle: Smoking habit, prolonged exposure to dust, wood, or metal particles may increase the risk.
Gender: More common in men than women.
Family history and genes: The genes a person inherits might make it more likely for them to develop IPF, especially if the genes carry mutations. E.g., mutation in gene MUC5B (which makes a mucus protein that helps clear harmful substances, like bacteria, from the lungs) increases the risk of IPF.

Treatment for IPF:

There is no cure for IPF, at present. However, medicines and other treatments (oxygen therapy and ventilator support) might help slow down the lung damage.
Lung transplant might be an option, however, it can cause major complications, such as infection or rejection of the new organ by the body.

Seasonal Outbreak of Influenza

Context: Every year, seasonal illnesses keep doctors and public health authorities busy. The outbreak of respiratory illnesses in children and adults caused by Influenza A ((H1N1), (H3N2), and Influenza B viruses, becomes more pronounced in winter in India.

Relevance of the Topic: Prelims: - Influenza; Types of Influenza Viruses

What is Influenza?

Influenza (flu) is a highly-contagious respiratory illness caused by influenza viruses that impacts the nose, throat and lungs.
Symptoms: Seasonal influenza is characterised by a sudden onset of fever, cough (usually dry), headache, muscle and joint pain, severe malaise (feeling unwell), sore throat and a runny nose.
Risks:
- Most people recover from fever and other symptoms within a week without requiring medical attention.
- But influenza can cause severe illness or deaths, especially in people at high risk. They include- young children and people with co-morbidities like asthma, diabetes, heart disease, weakened immune systems and neurological or neurodevelopmental conditions.

Types of Influenza Viruses:

Influenza viruses are of four different types: A, B, C and D.

Type A:
- Influenza A is associated with severe respiratory illness and deaths in humans. Only influenza type A viruses are known to have caused pandemics.
- They are further classified into subtypes according to the combinations of the proteins on the surface of the virus. E.g.,
  - H3N2 (HongKong Flu) and H1N1 (Swine Flu) viruses are subtypes of Influenza A virus.
  - H5N1 (Avian influenza/ Bird Flu) is also a subtype of the Influenza A virus that primarily infects birds but can also infect humans and other mammals.
Type B:
- Influenza B almost exclusively infects humans, and is less common than influenza A.

Type C:
- Detected less frequently and usually causes mild infections, thus does not present public health importance.
Type D:
- Primarily affects cattle and are not known to infect or cause illness in people.

Influenza viruses are constantly evolving, the factors include:

High population density, poor hygiene practices, weather conducive to the survival and spread of the virus increase the risk of flu transmission.
Indiscriminate antimicrobial use due to the absence of definitive diagnosis and influenza symptoms coinciding with other acute respiratory infections.
Low Vaccination rates as strategies for influenza prevention and control have not been prioritised by the Indian Medical Association. Influenza vaccine is not included into the government’s Universal Immunisation Programme.
Due to climate change, seasonal epidemics of influenza may shift spatially and temporally, with rising temperatures and abnormal rainfall patterns being contributing factors.

Way Forward:

Adult immunisation programmes in India must be leveraged for making Influeza vaccines available in the country. E.g., National Centre for Disease Control (NCDC) has recommended the prudent use of the Southern Hemisphere’s 2024 quadrivalent influenza vaccine.
Expansion of the Universal Immunisation Programme to include influenza vaccines can reduce community transmission, unnecessary antimicrobial prescriptions and superimposed bacterial infections that can complicate influenza.

What is Disease X?

Context: Disease X represents an unpredictable, novel threat that requires rapid global response and adaptation. This becomes significant due to increased interconnectedness of our world (with frequent international travel and trade), making it easier for localised outbreaks to escalate into pandemics, as seen with COVID-19.

Disease X?

Disease X is not a specific disease but is the name given to a potential novel infectious agent. It represents an illness which is currently unknown but could pose a serious microbial threat to humans in the future.
In 2018, the World Health Organisation (WHO) added Disease X to the ‘list of pathogens’ to prioritise preparation on the emerging diseases that do not yet have vaccines or drug treatments, and could give rise to a severe epidemic.
It could originate from Pathogen X, which could be a virus, a bacterium, a parasite, fungi, helminths, or even a prion (a misfolded protein capable of causing severe neurological diseases).

WHO’s priority list of Pathogens:

The list of pathogens is a strategic tool published by WHO in 2018 to focus global attention and resources on the most serious infectious disease threats.
This list identifies diseases that have:
- High mortality rates
- Epidemic or pandemic potential
- Lack of adequate preventive (vaccine) or therapeutic options.
The current list (not exhaustive ) includes: Ebola virus disease, Marburg virus disease, Lassa fever, Nipah virus, Rift Valley fever, Crimean-Congo haemorrhagic fever, Zika virus, Severe Acute Respiratory Syndrome (SARS), Disease X.

Significance: It helps policymakers, researchers, and health organisations prioritise efforts toward controlling the diseases (to guide research and development, allocate funding, and enhance preparedness).

Risk Factors for Disease X:

Zoonotic Spillover: Increased risk of zoonotic spillover due to human encroachment on wildlife habitats, deforestation, and the intensification of agriculture.
- Since 1940, researchers have identified more than 300 emerging infectious diseases, about 70% of which have zoonotic origins (transmitted from animals to humans).
Increasing Antimicrobial Resistance: Resistance acquired by any microorganism (bacteria, viruses, fungi, parasite) against antimicrobial drugs or treatments to which they were previously susceptible.
- Incomplete doses of medication, self-medication, inappropriate disposal of unused or expired medication in the environment.
- Using antibiotics in farm animals, herbicides may enrich AMR genes (ARGs) and Mobile genetic elements (MGEs) by altering soil microbiomes.
- Biofilms on microplastics and untreated solid and liquid waste can act as a reservoir of AMR microbes.
Risk of Bioterrorism and Accidental lab leaks. Beyond the WHO’s guidelines, there is no universal law, regulation or international oversight mandating even basic requirements, such as external independent inspections of biosafety laboratories (which host a range of pathogens).
Climate Change:
- Climate change is expanding the burden of infectious diseases (transmitted by insect vectors and through contaminated water). It is also pushing pathogens to adapt to new hosts and environments.
- With global warming there is a risk of thawing permafrost which harbours viruses up to a million years old (older than the human species).

Way Forward:

Need for robust surveillance systems to detect new outbreaks early and global alliance for developing its treatment. E.g., Coalition for Epidemic Preparedness Innovations (CEPI) has set a target of 100 days to develop, test and produce a new vaccine against pathogen X (COVID-19 vaccine took 326 days).
Investing in Research and Innovation: Utilising advances in genomic sequencing, artificial intelligence, and real-time data sharing as essential tools for developing diagnostics, therapeutics, and vaccines.
Strengthening healthcare infrastructure particularly in low- and middle-income countries.
Global Collaboration: Frameworks like the Nagoya Protocol (which ensure equitable sharing of benefits from genetic resources) could be expanded to include biological materials like pathogens. It would promote global collaboration, ensuring fair access to research and medical countermeasures during outbreaks.

Conclusion: While epidemiology cannot predict the exact moment or source of Disease X, it can help identify high-risk regions and behaviours. Governments must work together to share data, pool resources, and ensure equitable access to diagnostics, treatments, and vaccines.

Gene Therapy for Haemophilia

Context: The Department of Biotechnology (DBT) along with the Centre for Stem Cell Research (CSCR) at Christian Medical College (CMC), Vellore, Tamil Nadu has successfully executed a first-in-human gene therapy using lentiviral vectors to treat Haemophilia-A.

Relevance of the topic:

Prelims: Haemophilia; Gene Therapy Products; National Guidelines For Gene Therapy

Mains: Gene Therapy: Mechanism; Applications, Challenges

What is Haemophilia?

Haemophilia is a rare genetic severe bleeding disorder caused by the deficiency of clotting Factor VIII, leading to spontaneous internal and external bleeding episodes.
- People with Haemophilia have lower levels of clotting factors (proteins in blood that help it clot). This can lead to excessive bleeding, even after a minor injury.
It is an X-chromosome linked recessive disorder, which means that it is more common in males than in females. Females can carry the haemophilia gene, but they usually do not have symptoms unless they have two copies of the gene, one from each parent.
India bears the world’s second-largest burden of Haemophilia.
- It is a lifelong condition with no permanent cure.
- Current treatments involve frequent Factor VIII replacement therapy (to replace the deficient clotting factor through infusions).

What is Gene Therapy?

Gene therapy is a technique that seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use (treat or cure disease).
Gene therapies can work by several mechanisms:
- Inactivating a disease-causing gene that is not functioning properly.
- Replacing a disease-causing gene with a healthy copy of the gene.
- Introducing a new or modified gene into the body to help treat a disease.

Modes of Gene Therapy:

Germline Gene Therapy:
- This involves modifying genes in reproductive cells (sperm or egg), which means the changes would be passed onto future generations.
- Gene editing of embryonic cells is banned across the world (and in India by ICMR Guidelines 2019)

Somatic Gene Therapy:
- This involves modifying genes in any cell other than a reproductive cell. Changes made through somatic gene therapy affect only the treated individual and are not inherited by their offspring. This is the primary focus of current gene therapy research due to its safety and ethical considerations.

Gene Therapy Products:

Gene Therapy Products (GTP) are biological substances designed to introduce genetic material into a patient's cells to treat or prevent a disease.

Key Components of GTP:

Therapeutic Gene: This is the specific genetic material intended to treat the disease.
Vector: A carrier that delivers the therapeutic gene into the target cells. This can be a virus (viral vector) or a synthetic carrier (non-viral vector).
Other Components: Depending on the specific product, additional components may be included, such as promoters, enhancers, or markers to optimise gene expression.

Types of Gene Therapy Products:

Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors:
- Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses.
- Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors/vehicles to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.

Applications of Gene Therapy:

Cardiovascular Diseases: Gene therapy is being explored to treat conditions like heart failure, coronary artery disease, and arrhythmias.
Cancer: This is a major focus area for gene therapy, with various approaches being investigated, including CAR T-cell therapy, tumour suppressor gene therapy, and oncolytic viruses.
Genetic Disorders: Gene therapy holds great promise for treating genetic diseases like cystic fibrosis, hemophilia, and muscular dystrophy by correcting the underlying genetic defect.
Neurological Disorders: Conditions like Parkinson's disease, Alzheimer's disease, and spinal cord injuries are being targeted with gene therapy to restore neuronal function.
Infectious Diseases: Gene therapy is being explored as a potential treatment for HIV/AIDS and other infectious diseases by enhancing the immune response.

Challenges involved in Gene Therapy:

Delivery of genes: Effectively getting the genetic material to the target cells can be difficult.
Immune response: The body might reject the introduced genetic material.
Long-term effects: The long-term consequences of gene therapy are still being studied.
Ethical Concerns: Germline Gene Therapy raises significant ethical concerns (designer babies, unintended consequences on future generations) and is currently banned in many countries.

National Guidelines For Gene Therapy:

The Indian Council of Medical Research (ICMR) released National Guidelines for Gene Therapy Product Development and Clinical Trials in 2019. The guidelines are a crucial framework for the advancement of gene therapy in India.
Purpose: To ensure the ethical, scientific, and safe conduct of gene therapy clinical trials and promote the development of gene therapies for treating genetic and rare diseases.
Scope: Covers all aspects of gene therapy product development, from preclinical testing to clinical trials and post-market surveillance.
Ethical Emphasis: Strong focus on patient safety, informed consent, and ethical considerations.
GTAEC: Establishes the Gene Therapy Advisory and Evaluation Committee (GTAEC) to oversee gene therapy activities.
Focus on Rare Diseases: Aims to address the unmet needs of patients with rare genetic disorders.

Mechanism used in the latest Gene Therapy to treat Haemophilia:

The gene therapy approach uses a lentiviral vector to introduce a normal copy of the Factor VIII gene into autologous haematopoietic stem cells (HSCs).
- Lentiviral vectors are a type of viral vector that can be used to transfer genetic material into cells for gene therapy.
These modified HSCs generate blood cells capable of producing functional Factor VIII over extended periods, thus terminating the need for repeated infusions.

Extrachromosomal DNA

Context: Extrachromosomal DNA (ecDNA) is now taking centerstage in the complex field of cancer biology. Recent research studies explore how ecDNA is formed and it contributes to the progression of cancer and drug resistance.

Relevance of the Topic: Prelims- Extrachromosomal DNA (ecDNA); Mitochondria (mtDNA); Cell-free DNA.

Background: Basics of Cell and DNA

Each cell in the human body has 23 pairs of chromosomes (46 total chromosomes). Chromosomes are thread-like structures found in the nucleus of cells and are made up of DNA and proteins.
DNA (deoxyribonucleic acid) is a molecule present in the nucleus of a cell that carries genetic information in the form of genes. Genes encode a complete set of instructions for building and maintaining an organism.
Majority of DNA is found in the chromosomes (nuclear DNA), however, DNA can also be found as:

extrachromosomal DNA (ecDNA)
mitochondria (mtDNA)
cell-free DNA (cfDNA)

What is extrachromosomal DNA (ecDNA)?

Extrachromosomal DNA (ecDNA) is any DNA that is found off the chromosomes (either inside or outside the nucleus of a cell).
Formation of ecDNA:
- There are some natural processes that can damage DNA. For example, in some cancers, chromothripsis occurs (the chromosomes are broken and rearranged). Cells can also make mistakes when making new copies of DNA.
- Such processes could cause a small part of the DNA to break away from the main chromosome and form a circular structure that floats freely inside the nucleus. This is ecDNA.

New Research related to ecDNA:

Early observation: ecDNA was discovered in cancer cells around 50 years ago. At that time, it was believed to be present in only 1.4% of tumours, and so was ignored.
Later observations: More sophisticated genomic techniques later revealed that ecDNA is present in nearly 40% of cancer cell lines and in up to 90% in patient-derived brain tumour samples, revealing its pivotal role in cancer biology.
ecDNA and Cancer growth: (Gist: ecDNA may amplify oncogene expression and thus, lead to higher prevalence of Cancer)
- ecDNA present in tumours often contains multiple copies of oncogenes (mutated genes capable of causing cancer) that are required to activate tumour growth.
- Unlike chromosomal DNA (which is fixed), ecDNA moves freely and can interact with other ecDNA to form hubs (concentrated zones where oncogenes are highly expressed).
- During the transcription process (when cells transcribe ecDNA to mRNA), ecDNA amplifies oncogene expression, making certain oncogenes become four-times more abundant in the cell, than if the DNA came from the chromosomes.
- This anomaly can cause rapid evolution of tumours, onset & spread of cancer and cause drug-resistance.
- Additionally, the prevalence of ecDNA rose after treatments like chemotherapy and could lead to cancer relapse.

1. Cell-free DNA:

Cell-free DNA (cfDNA) are the fragments of DNA found in bodily fluids (such as blood, urine, saliva, and cerebrospinal fluid).
They are released into the bloodstream by cells that underwent programmed cell death or an unplanned cell death (due to any injury or disease).
These degraded (non-functional) fragments of nucleic acids do not possess the ability to replicate or carry out cellular processes.
However, cfDNA can carry genetic information from the cells they originated from, making them a valuable source for various applications.

Important applications of cfDNA:

Non-invasive prenatal testing to screen for chromosomal abnormalities in a developing foetus like Down syndrome, Edwards syndrome etc.
Aid in early-cancer detection by providing information about genetic mutations and alterations present in tumour cells.
Aid in diagnosis of infectious diseases and in forensics.
Used as a biomarker for neurological disorders like Alzheimer’s disease etc.
Provide an early indication of graft rejection in patients who underwent organ transplants.

2. Mitochondrial DNA (mtDNA):

Some DNA is also present in the mitochondria (mtDNA).
- Mitochondria are cellular organelles found in the cytoplasm.
- They are called powerhouse of the cell as they generate most of the cell's energy currency- ATP (adenosine triphosphate).
In humans, mtDNA is circular and much smaller (about 16,500 base pairs) compared to nuclear DNA.
mtDNA codes for a small number of genes, essential for the proper functioning of mitochondria.
Inheritance: mtDNA is inherited almost exclusively from the mother. (Nuclear DNA comes from both parents)
Mitochondrial DNA is more prone to mutations compared to nuclear DNA as it is exposed to free radicals generated during energy production, which can damage DNA.
When Mitochondria are impaired they do not produce sufficient energy. It causes inherited conditions like heart problems, liver failure, brain disorders, blindness and muscular dystrophy. There is no cure for mitochondrial DNA diseases at present.
Mitochondrial Donation Treatment (three parent baby): Mitochondrial donation involves replacing unhealthy mitochondria in the mother with healthy mitochondria from a donor through in-vitro fertilisation (IVF). This would avoid passing faulty mitochondria to the child.

DNA Profling

Context: DNA Profiling has been an important tool in solving cases involving forensic science, medical investigations and familial disputes. However, the technology also raises some concerns about its ethical implications and privacy breaches.

Relevance of the Topic: Prelims- DNA Profiling: Applications & Challenges

What is DNA Profiling?

DNA profiling/DNA Fingerprinting is the technique used to identify individuals by analysing the unique patterns in their DNA.
The process involves analysing the Short Tandem Repeats (STRs) which are highly specific to each individual (except identical twins).

The Basics of Cell and DNA:

Each cell in the human body has 23 pairs of chromosomes (46 total chromosomes).
- Chromosomes are thread-like structures made of DNA and proteins, found in the nucleus of cells.
- One chromosome of each pair is inherited via the mother’s egg and the other via the father’s sperm.
DNA (deoxyribonucleic acid) is a molecule that carries genetic information. It is composed of four chemical bases: adenine (A), cytosine (C), guanine (G), and thymidine (T).
- Base-pairing: A pairs with T, and G pairs with C, to form a double-helical structure.
The human genome consists of 3.2 billion base-pairs across 23 pairs of chromosomes. At several locations in the genome, some short DNA sequences are repeated multiple times, called short tandem repeats (STRs).
- For example, one strand of an STR locus might have multiple repeats of GGCCA (GGCCAGGCCAGGCCA…).
The DNA profile of a person is simply the number of times these sequences are repeated. The number or pattern of repetition is unique to each individual, which can be analysed by DNA profiling.

How is a DNA Fingerprint produced?

Isolation: Extraction of DNA from a biological sample (E.g., blood, hair, saliva, semen etc.)
Fragmentation: Break the DNA into smaller pieces using enzymes.
Amplification: Make multiple copies of the DNA fragments by Polymerase Chain Reaction (PCR).
Separation: Arrange DNA fragments by size using techniques such as gel electrophoresis.
Comparison: Match the DNA profile to reference samples of DNA for identification.

Applications of DNA Profilling:

Paternity determination.
Criminal forensics (help solve crimes using DNA present at crime scene).
Identification of victims in mass disasters.
Establishing donor-recipient compatibility in organ transplants.
Identification of alleles associated with particular genetic disorders (E.g., cystic fibrosis)
Compare different species for classification purposes.

Challenges associated with DNA Profilling:

Cannot be used to identify identical twins.
Reliability of DNA profiling depends on quality of the sample, expertise in laboratory analysis. The process is not infallible and various factors (like sample contamination, degradation, or mishandling) can impact the results.
Storage of DNA profiles can be an invasion of privacy, and risk of theft of DNA profiles from a database.
Risk of Racial and Communal profiling.

H5N1 mutations raise risk of Human Infections

Context: A global outbreak of H5N1 (a highly pathogenic avian influenza virus) has been spreading across the world since late 2020. Recent human cases of H5N1 infections have raised alarms regarding its potential to turn into pandemic.

About Influenza:

Influenza (flu) is a highly-contagious respiratory illness caused by influenza viruses.
Symptoms of influenza include acute onset of fever, cough, sore throat, body aches and fatigue.

Influenza viruses are of four different types: A, B, C and D.

i. Type A:

Influenza A is associated with severe respiratory illness and deaths in humans.
Only influenza type A viruses are known to have caused pandemics.
They are further classified into subtypes according to the combinations of the proteins on the surface of the virus. E.g.,
- H3N2 (HongKong Flu) and H1N1 (Swine Flu) viruses are subtypes of Influenza A virus.
- H5N1 (Avian influenza/ Bird Flu) is also a subtype of the Influenza A virus that primarily infects birds, but can also infect humans and other mammals.

ii. Type B: Influenza B almost exclusively infects humans, and is less common than influenza A.

iii. Type C: Detected less frequently and usually causes mild infections, thus does not present public health importance.

iv. Type D: Primarily affects cattle and are not known to infect or cause illness in people.

H5N1 Virus (Avian influenza/ Bird Flu):

H5N1 (Avian influenza/ Bird Flu) is a subtype of the Influenza A virus that predominantly infects birds, but can also infect humans and other mammals.
The virus can infect people in close contact with infected birds, including dairy or poultry farm workers.
Recent human cases of H5N1 in Canada and California have increased concerns about the possible mutations in the virus that could facilitate human-to-human transmission.
- Genome sequencing identified a particular mutation which is linked to faster replication of the virus in human cells and greater severity of illness.
- The findings raise concerns about the potential of the virus to cause more severe respiratory illness in humans.

Influenza viruses are constantly evolving, the factors include:

High population density, poor hygiene practices, weather conducive to the survival and spread of the virus increase the risk of flu transmission.
Indiscriminate antimicrobial use due to the absence of definitive diagnosis and influenza symptoms coinciding with other acute respiratory infections.
Low Vaccination rates as strategies for influenza prevention and control have not been prioritised by the Indian Medical Association. Influenza vaccine is not included into the government’s Universal Immunisation Programme.
Due to climate change, seasonal epidemics of influenza may shift spatially and temporally, with rising temperatures and abnormal rainfall patterns being contributing factors.

India’s corneal blindness problem

Context: India is facing an acute shortage of corneas required for transplantation, whereas the cases of corneal blindness in the country are on the rise.

Relevance of the topic:

Prelims: Cornea; Transplantation of Human Organs and Tissues Act (THOTA), 1994

Mains: Ethical issue- balancing individual consent and public good in medical practices.

Corneal Blindness in India

Prevalence: Corneal blindness, a leading cause of vision impairment in India, with the country seeing an estimated 20,000 to 25,000 new cases every year.
Corneal blindness is vision loss due to damage or scarring of the cornea (the eye's transparent outer layer).
- Reasons include- Infectious diseases like keratitis, eye trauma, injuries, congenital conditions and deficiencies like vitamin-A.
- Without timely treatment, it can lead to irreversible blindness.
Annual Requirement: Approximately 1,00,000 corneal transplants.
Availability: Only 30% of corneal transplants demand is met.
Infrastructure Deficit:
- India has only 12–14 high-functioning eye banks against the required 50 facilities.
- Shortage of skilled corneal surgeons with a current need for 500 active specialists.

Policy Proposals: Presumed Consent vs. Required Request:

The Ministry of Health is proposing a policy to allow corneal retrieval from deceased patients without prior family consent, aiming to address the shortage.
It will require a ‘presumed consent’ amendment to the Transplantation of Human Organs and Tissues Act (THOTA), 1994 to allow cornea retrieval from all eligible deaths in hospitals.

1. Presumed Consent:

Definition: All deceased individuals are treated as donors unless they have explicitly opted out.
Advantages: Quicker organ-retrieval, the process is simplified by by-passing the requirement of consent from the next-of-kin. (Corneas need to be retrieved within eight to 10 hours after death)
Issues: Undermines public trust due to lack of explicit consent.

2. Required Request:

Definition: Seeking consent explicitly from the next-of-kin of the deceased person even if a presumed consent law exists.
Advantages: Builds trust between donors, recipients and the healthcare system.
Challenges: Time-consuming and requires counselling at hospitals.

India’s Hospital Cornea Retrieval Programme (HCRP):

India has a successful model of ‘required request’ corneal donation: a hospital cornea retrieval programme (HCRP).
In an HCRP, a grief counsellor approaches the kin of the deceased and initiates a conversation, gently motivating them to consider a donation. The donation is processed only after receiving explicit consent from the kin.
- Of the 1,40,000 corneas harvested by the Ramayamma International Eye Bank in Hyderabad, over 70% have come from HCRP.

Way Forward

Programs focusing on eye health education and nutritional support, particularly with Vitamin-A supplementation for vulnerable populations.
Widespread educational campaigns using media and community events to inform the public about the significance of eye donation, the processes involved, and its positive impact.
Building high-functioning eye banks, training corneal surgeons and building specialised units for grief-counseling in general hospitals.
Enhance collaboration between public health bodies, NGOs, and private healthcare providers.

It is therefore possible for India to eliminate avoidable corneal vision loss by investing in a consent-driven donation paradigm, 50 high-functioning eye banks, and by activating 500 corneal surgeons.

Pills that can replace injections/ New Ingestible Capsules for Drug Delivery

Context: A team of researchers has developed new ingestible capsules that release a burst of drugs directly inside the stomach or other parts of the digestive system. These capsules can offer an alternative to traditional methods like injections for delivering drugs such as insulin.

Relevance of the topic: Prelims- General idea about new ingestible capsules; Biobioavailability

Advantages of injections over pills:

Injections are usually used to administer hormones, vaccines, antibodies, or cancer treatments because drugs are usually made of larger biological molecules.
If swallowed as pill, the larger biological molecules are often quickly destroyed by digestive enzymes or the liver before they can work, limiting their efficacy and increasing the likelihood of potential side effects.

Problems with injections:

Despite their advantage over pills, injections can lead to infection, skin irritation, and other side effects.
They can also cause discomfort to patients, making oral alternatives more desirable.

About New Ingestible Capsules

Development: The inspiration for their development came from cephalopods such as squids and cuttlefish, which use jet propulsion mechanisms to move or release ink.
- Researchers adapted this jetting principle to distribute drugs in the gastrointestinal (GI) tract.
- Jet propulsion mechanism ensures that more medication is absorbed before the body breaks it down.

Mechanism:
- Capsules use compressed carbon dioxide or tightly coiled springs to generate the force needed to propel liquid drugs out of the capsule.
- The gas or spring is kept in a compressed state by a carbohydrate trigger. This trigger dissolves when exposed to humidity or an acidic environment in the stomach. When the trigger dissolves, the gas or spring is allowed to expand, and eject drugs out of the capsule.

Advantage of the capsule:
- The new capsules have shown high efficiency in bioavailability (the body’s ability to absorb and use drugs) in animal models compared to earlier attempts.

What is Alzheimer's Disease?

Context: According to a new study, semaglutide, the active ingredient in popular blood sugar control and weight loss drugs, can reduce the risk of Alzheimer’s disease (AD) in people with type 2 diabetes.

Major Highlights:

Early research on semaglutide identifies a number of ways in which it might benefit the brain, such as:
- Lowering toxic effects of certain proteins linked to AD and improving how brain cells use glucose for energy.
- Reducing the buildup of harmful plaques and tangles associated with Alzheimer’s.
- Reducing neuro-inflammation, which is commonly linked to Alzheimer.
Specifically, it was found to reduce the risk of a first-time Alzheimer’s diagnosis by 40% to 70%.

Alzheimer’s disease:

Alzheimer’s disease is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die. Alzheimer’s causes a gradual decline in memory, thinking, behaviour, and social skills, and it is the most common cause of dementia.
Causes: The disease is thought to be caused by the abnormal build-up of proteins in and around brain cells.
- One of the proteins involved is called amyloid, deposits of which form plaques around brain cells.
- The other protein is called tau, which is a deposit that forms tangles within brain cells.
Symptoms: Early signs include forgetting recent events/conversations. Later, the person will develop severe memory impairment and lose the ability to carry out everyday tasks. In the advanced stages, complications from severe loss of brain function result in death.
Treatment: Currently, there is no cure for Alzheimer’s disease, but certain medications can temporarily slow the worsening of dementia symptoms.
- Traditionally, Alzheimer’s has been managed largely using cognitive and lifestyle interventions.
- Recently, the US Food and Drug Administration (FDA) has approved two treatments — Biogen’s Leqembi and Eli Lilly’s Kisunla — that marginally slow the progression of AD by targeting the disease’s hallmark amyloid plaques in the brain. But these can cause serious side effects, including brain swelling and brain bleeding.