Subject: Biotech and Medical Sciences

Central Idea

• Researchers worldwide are increasingly using Cell-free DNA (cfDNA) as a valuable tool to better comprehend human diseases, improve diagnosis, monitoring, and prognosis.

What is Cell-free DNA?

• CfDNA refers to small fragments of nucleic acids that are released from cells and found outside the cell in body fluids.
• Its discovery dates back to the late 1940s when it was first observed in the blood of pregnant women.
• cfDNA can be generated and released from cells in various situations, such as cell death and other physiological processes.
• The release of cfDNA is associated with several disease processes, including autoimmune diseases like systemic lupus erythematosus.

How is it different from normal DNA?

Applications of CfDNA

Recent Advances in Therapeutics

• GEMINI Test: Researchers at Johns Hopkins Kimmel Cancer Centre developed a new test called ‘GEMINI’ that uses cfDNA for early cancer detection. By analyzing genetic mutations and using machine learning, they achieved over 90% accuracy in detecting lung cancer, even in early-stage cases.
• Potential Impact: Early detection of cancers using cfDNA could significantly improve patient outcomes and survival rates.

Central Idea

• India has taken its first step towards introducing Controlled Human Infection Studies (CHIS), a research model widely used in other countries for vaccine and treatment development.
• The Indian Council of Medical Research’s (ICMR) Bioethics Unit has prepared a consensus policy statement open for public comment, addressing the need, benefits, and ethical challenges associated with CHIS.

What is Controlled Human Infection Studies (CHIS)?

• CHIS also known as human challenge trials, are scientific studies conducted to deliberately expose healthy human volunteers to infectious agents under controlled conditions.
• The primary objective of these studies is to gain a better understanding of the pathogens’ behavior, human immune response, and to test potential vaccines, treatments, or preventive measures against the infection.

Key points about Controlled Human Infection Studies (CHIS) include:

1. Informed Consent: Volunteers participating in CHIS must provide informed consent, fully understanding the potential risks and benefits associated with their participation.
2. Types of Pathogens: CHIS can be used to study various infectious agents, such as viruses (e.g., influenza, dengue, Zika), bacteria (e.g., cholera, typhoid), and parasites (e.g., malaria).
3. Vaccine Development: CHIS plays a crucial role in vaccine development by providing controlled environments to assess the efficacy of candidate vaccines and their ability to induce protective immune responses.
4. Controversy: The use of CHIS has sparked ethical debates about balancing potential risks to participants against potential benefits to public health.

Ethical Concerns Surrounding CHIS in India

• Delicate Ethical Balance: CHIS is considered ethically sensitive due to concerns about deliberate harm to participants, fair compensation, third-party risks, and withdrawal from the study, and involving vulnerable participants.
• Streamlined Ethics Review: ICMR acknowledges the need for a specialized ethics review process with additional oversight and safeguards to protect study participants.
• Deterrents and Unique Context: Technical, clinical, ethical, and legal challenges deterred India from adopting CHIS earlier, partly influenced by the nation’s unique socio-cultural context.

Potential Benefits of CHIS in India

• High Disease Burden: India faces a significant burden of morbidity and mortality from infectious diseases, contributing about 30% of the disease burden in the country.
• Novel Insights and Efficiency: CHIS offers unique insights into disease pathogenesis and enables accelerated and cost-effective outcomes with smaller sample sizes compared to large clinical trials.
• Social Value: CHIS can contribute to public health response, healthcare decision-making, policies, economic benefits, improved pandemic preparedness, and community empowerment.

Encouraging Collaboration and Expertise

• Complex Nature of CHIS: ICMR highlights the complexity of CHIS and suggests that collaborations between researchers, institutions, organizations, and countries may be necessary to ensure the right expertise is available.
• Crucial Role in Advancing Scientific Understanding: The ICMR Bioethics Unit’s consensus policy statement aims to address ethical concerns associated with CHIS, acknowledging its potential role in advancing the scientific understanding of infectious diseases and accelerating treatment strategies.

Public Consultation and Future Directions

• Open for Public Consultation: The ICMR’s consensus policy statement on CHIS is open for public consultation until August 16 to gather input from stakeholders and experts.
• Striving for Ethical Research: ICMR emphasizes its commitment to conduct CHIS in India while ensuring ethical principles are upheld and human participants are protected.

Conclusion

• The introduction of CHIS in India is a significant step towards advancing medical research and finding cost-effective solutions for infectious diseases.
• Public consultation and expert collaborations will help shape the future direction of CHIS research in India and contribute to scientific progress and improved healthcare outcomes.

Central Idea

• Donanemab, a drug in trials has shown significant potential in slowing cognitive decline in individuals with early Alzheimer’s.

What is Alzheimer’s Disease?

• Alzheimer’s disease is a progressive and irreversible neurological disorder.
• Beta-amyloid, a protein that is crucial for brain function, turns toxic in Alzheimer’s patients, forming clumps that disrupt brain cell connections, leading to cognitive issues like memory loss.
• These protein deposits disrupt communication between neurons, leading to their deterioration and death.
• Early signs include forgetfulness, difficulty finding words, problem-solving challenges, confusion, and disorientation.
• The exact cause of Alzheimer’s is not fully understood but is believed to involve genetic, environmental, and lifestyle factors.
• Family history, genetic mutations, head injuries, cardiovascular disease, and certain lifestyle factors are also risk factors.

Donanemab: An antedote

• Development: Donanemab is a drug developed by Eli Lilly and aims to treat individuals with early Alzheimer’s disease.
• Targeting Amyloid Plaques: The drug targets a common hallmark of Alzheimer’s disease: amyloid plaques in the brain.

Breakthrough in Slowing Cognitive Decline

• Alarming Burden: With an estimated 14 million cases of dementia, including Alzheimer’s, expected in India by 2050, the need for effective treatments is urgent.
• Phase III Trial: In a phase III trial, Donanemab demonstrated promising results, slowing cognitive decline by 35% compared to a placebo.
• Significance: This marks a significant milestone in Alzheimer’s research, as it is the second drug, within a year, to show effectiveness in checking cognitive decline in early-stage Alzheimer’s patients.
• Limitations: It is essential to note that Donanemab and the previous drug do not stop or reverse Alzheimer’s disease. However, slowing cognitive decline can significantly improve the quality of life for affected individuals and their families.

Central Idea

• Viruses have had a significant impact on human history, causing deadly outbreaks of diseases.
• However, not all viruses are harmful, and scientists are discovering the importance of the virome (bacteriophages).

What are Virome?

• What is it: They are the collection of viruses in our bodies contributing to our health, similar to the bacterial microbiome.
• Bacteriophages: The majority of viruses inside us are bacteriophages, which kill bacteria in our microbiomes without affecting human cells.
• Vast in Numbers: Our bodies host around 380 trillion virus particles, 10x more than the number of bacteria.
• Beneficial Viruses: Some viruses play beneficial roles, such as killing cancer cells, aiding immune system training, fighting pathogens, and regulating gene expression during pregnancy.

Bacteriophages and Phage Therapy

• Bacteriophages’ Mechanism: Bacteriophages hunt down bacteria, attach to their surface, inject viral DNA, and replicate inside the bacteria before causing the bacterial cell to burst and release new viral particles.
• Historical Background: In the early 20th century, scientists explored phages as potential treatments for bacterial infections, but antibiotic development overshadowed this research.
• Antibiotic Resistance: With the rise of antibiotic-resistant bacteria, scientists are revisiting phage therapy as an alternative to combat bacterial infections.
• Advantages of Phages: Phages effectively target multi-resistant pathogens, are precise in eliminating bacterial strains, and do not disrupt the gut microbiome like antibiotics do.

Phage Therapy in Practice

• Historical Use: Phage therapy persisted in countries like Georgia, Ukraine, and Russia, where antibiotics were scarce. These regions have witnessed successful treatment outcomes against antibiotic-resistant infections.
• Expanding Use: Phage therapy is gaining attention in countries like Belgium, the US, and Germany, with specialized therapy centres and calls for increased exploration and utilization.
• Challenges and Safety: Standardization of therapy and tailoring phages to specific bacteria causing the infection remain challenges. However, phage therapies have a good safety record, and human bodies can tolerate them well.

Future Prospects

• Complementary Approach: Phages are unlikely to replace antibiotics but could be used in combination to enhance antibiotic effectiveness, particularly against resistant bacterial strains.
• Research and Clinical Projects: Further large-scale research and clinical projects are recommended to establish effective phage therapies for different types of infections.

Central Idea

• Europe is currently experiencing a heatwave and wildfires, leading to concerns about the spread of viruses that are typically not found in colder climates.
• The WHO has issued an alert regarding the Crimean-Congo haemorrhagic fever (CCHF), a potentially fatal infection transmitted by ticks.

What is CCHF?

• CCHF is a viral haemorrhagic fever primarily transmitted by ticks.
• It can also be contracted through contact with viraemic animal tissues during animal slaughter.
• CCHF outbreaks can lead to epidemics with a high case-fatality ratio (10-40%) and pose challenges for prevention and treatment.

Transmission and Hosts

• The virus exists in the tick family of insects.
• Animals such as cattle, goats, sheep, and hares serve as amplifying hosts for the virus.
• Humans can contract CCHF through contact with infected ticks or animal blood.
• The virus can also be transmitted between humans through contact with infectious blood or body fluids.
• Migratory birds can host ticks, allowing the virus to spread over long distances.

Symptoms and Treatment

• Common symptoms of CCHF include fever, muscle aches, dizziness, neck and back pain, headache, sore eyes, and sensitivity to light.
• Early symptoms may also include nausea, vomiting, diarrhea, abdominal pain, and sore throat, followed by mood swings and confusion.
• Later stages may involve sleepiness, depression, and lassitude.
• There is no vaccine available for CCHF in humans or animals, and treatment focuses on managing symptoms.
• The antiviral drug ribavirin has been used to treat CCHF infection with some apparent benefit.

Spread of CCHF in Europe

• CCHF is endemic to Africa, the Balkan countries, the Middle East, and parts of Asia.
• In 2016, Spain reported the first fatality from CCHF in Europe.
• Scientists warn that CCHF, which can have a fatality rate between 10% and 40%, is spreading northward and westward in Europe.
• Cases of CCHF have been reported in Spain, Russia, Turkey, and the UK.

Reasons for this spread

• Disrupted temperature patterns due to climate change are creating favorable conditions for pathogens.
• CCHF ticks are moving northward through Europe due to longer and drier summers caused by climate change.
• Climate change contributes to the spread of diseases by expanding tick habitats, altering water habitats, and facilitating the movement of animals and human interactions.

Central Idea

• Researchers in India are collaborating to develop an affordable treatment for Duchenne Muscular Dystrophy (DMD), a rare and incurable genetic disorder.
• The Indian Institute of Technology (IIT), Jodhpur, is collaborating to develop affordable therapeutics for DMD.

What is DMD?

• DMD is a progressive muscle degeneration disorder caused by alterations in the dystrophin protein.
• It is the most common and fatal type of muscular dystrophy, primarily affecting boys.
• It leads to progressive muscle degeneration, weakness, and eventually wheelchair dependency, assisted ventilation, and premature death.

Symptoms and Impact of DMD

• Muscle Weakness: Muscle weakness is the primary symptom of DMD, initially affecting proximal muscles and later distal limb muscles. Difficulties in jumping, running, and walking are common.
• Other Symptoms: Enlargement of calves, a waddling gait, lumbar lordosis (inward curve of the spine), and later heart and respiratory muscle involvement. Pulmonary function impairment and respiratory failure may occur.

Current Challenges

• Costly treatment: Current therapeutic options for DMD are minimal and expensive, with costs reaching up to Rs 2-3 crore per child per year.
• Limited Treatment Options: The treatments are predominantly imported, making them financially unattainable for most families.

Efforts to Develop Affordable Therapeutics

[A] Antisense Oligonucleotide (AON)-Based Therapeutics

• The IIT Jodhpur researchers are working on enhancing the efficacy of AON-based therapeutics.
• AONs can mask specific exons in a gene sequence, addressing the challenges faced in DMD patients.
• Personalized medicine is necessary due to the variations in mutations among DMD patients.

[B] Clinical Trials and Molecular Tags

• The research team has received approval from the Drugs Controller General of India (DCGI) to conduct multi-centric clinical trials on AON-based exon skipping in DMD patients.
• They are also working on reducing the therapeutic dose of AON through new molecular tags.

Central Idea

• Leptospirosis has emerged as an important infectious disease in the world today.
• It is a potentially fatal zoonotic bacterial disease that tends to have large outbreaks after heavy rainfall or flooding.

What is Leptospirosis?

• Leptospirosis is a zoonotic bacterial disease that poses a significant global health threat, particularly after heavy rainfall or flooding.
• It affects millions of people annually, with a high mortality rate, and its burden is expected to increase in the future.
• The disease is caused by the bacterium Leptospira interrogans, primarily transmitted from animals to humans.

Disease Transmission and Risk Factors

• Disease transmission: Leptospira is shed in the urine of infected animals, contaminating soil and water.
• Carriers: Both wild and domestic animals, including rodents, cattle, pigs, and dogs, can transmit the disease.
• Human exposure: Direct contact with animal urine or indirectly through contaminated soil and water poses a risk.
• Occupational hazards: Agricultural workers, animal handlers, and those in sanitary services are at an increased risk.
• Recreational activities: Engaging in water-based activities in contaminated lakes and rivers can also raise the risk.

Symptoms and Misdiagnosis

• Range of symptoms: Leptospirosis symptoms vary from mild flu-like illness to life-threatening conditions affecting multiple organs.
• Misdiagnosis challenges: Symptoms mimic other diseases like dengue, malaria, and hepatitis, leading to underreporting and limited awareness.
• Limited access to diagnostics: Lack of reliable diagnostic tools hinders accurate disease detection.
• Lack of environmental surveillance: Insufficient monitoring of the environment contributes to underestimating the disease burden.

Misconceptions and Preventive Measures

• Reservoir hosts: Rats are not the sole cause; various animals act as reservoir hosts.
• Environmental factors: Humidity and extreme weather events like floods increase the risk of exposure.
• Sanitary conditions: Poor waste management, high density of stray animals, and inadequate sanitation facilities contribute to the disease spread.
• Prevention strategies: Adopting a ‘One Health’ approach involving humans, animals, and the environment is crucial.
• Personal protective equipment: People working with animals or in flooded areas should use gloves and boots.
• Animal health and prevention: Ensuring sanitary animal-keeping conditions reduces the risk of leptospirosis transmission.
• Health education and awareness: Promoting proper hygiene practices, educating about the disease, and improving health literacy are essential preventive measures.

Central Idea

• The cancer research arm of the World Health Organization (WHO) is reportedly considering listing aspartame, a popular sugar substitute ‘Aspartame’ as “possibly carcinogenic to humans.”
• This potential listing by the International Agency for Research on Cancer (IARC) has generated controversy as it contradicts previous studies that found no evidence linking aspartame to cancer.

What is Aspartame?

• Aspartame is widely used as an artificial sweetener in various food and beverage products.
• It is made from the dipeptide of two amino acids, L-aspartic acid and L-phenylalanine.
• It is approximately 200 times sweeter than table sugar and is commonly used in diet soft drinks, sugar-free gum, and other sugar-free products.
• It is favored by those seeking to reduce calorie intake or manage diabetes.

Safety Record and Regulatory Approvals

• Aspartame has undergone extensive studies over 40 years, with over 100 studies finding no evidence of harm caused by its consumption.
• The US Food and Drug Administration (FDA) has permitted its use in food since 1981, and it has been reviewed multiple times for safety.
• The European Food Safety Authority (EFSA), as well as national regulators in various countries, also deem aspartame safe for consumption.
• However, individuals with phenylketonuria (PKU), a rare genetic disorder, should avoid aspartame due to the presence of phenylalanine.

Controversies and Impact of WHOs Listings

• Past IARC rulings have raised concerns, led to lawsuits, and influenced manufacturers to seek alternatives due to public confusion.
• The potential listing of aspartame as “possibly carcinogenic” by the IARC contradicts previous scientific consensus on its safety.
• Critics argue that IARC assessments can be confusing to the public and may create unnecessary fear and misinformation.