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A Lung in the Lab: How IISc 3D Model May Speed Up TB Cures

IISc 3D Model May Speed Up TB Cures

Tuberculosis (TB) remains one of the world’s deadliest infectious diseases, and India carries the heaviest burden. Every year, millions of Indians are diagnosed with TB, including drug-resistant forms that are difficult and costly to treat. While medicines exist, progress in TB treatment has been slow. One major reason is that scientists have struggled to study TB accurately in laboratories.

For decades, TB research has relied on flat, two-dimensional (2D) cell cultures or animal models. These systems do not truly reflect how TB behaves inside the human lung. Now, researchers at the Indian Institute of Science (IISc), Bengaluru, have developed a new three-dimensional (3D) lung-like model that could significantly improve how TB is studied and how new drugs are tested.

This innovation marks an important step in India’s fight against TB and aligns with global efforts to modernise drug discovery.

IISc 3D Model May Speed Up TB Cures

Why Studying TB Has Been So Difficult

TB is caused by the bacterium Mycobacterium tuberculosis, which mainly infects the lungs. Inside the human body, the bacteria interact with immune cells, fat molecules, oxygen gradients, and lung tissue structure in complex ways. However, traditional lab models fail to recreate this environment.

In 2D models, human cells grow on flat plastic surfaces. These conditions are far removed from the soft, spongy structure of lung tissue. As a result, TB bacteria behave differently, and drug responses seen in the lab often do not match what happens in real patients.

Animal models, such as mice, are another option, but they come with ethical concerns, high costs, and biological differences from humans. Some TB drugs that work in animals fail in human trials, leading to wasted time and resources.

 

The IISc Breakthrough: A 3D Lung-Like Model

To overcome these limitations, IISc researchers created a 3D model using a soft collagen-based hydrogel. Collagen is a natural protein found in human connective tissue and closely resembles the physical and biochemical properties of lung tissue.

In this model, infected human immune cells are embedded inside the gel. This allows both the host cells and TB bacteria to behave more realistically, similar to what happens in the lungs of TB patients.

The results were striking. The researchers observed key TB features that are usually absent in 2D models. These included fat-filled immune cells and clusters of TB bacteria, both of which are hallmarks of real TB infection.

 

Why This Model Is a Big Deal for Drug Testing

One of the most important findings was related to the TB drug Pyrazinamide. This medicine is a core component of standard TB treatment, but it often shows weak or inconsistent results in conventional lab models.

Using the new 3D system, researchers were able to clearly demonstrate Pyrazinamide’s effectiveness. This confirms that the model can capture drug responses that are otherwise missed.

According to the scientists involved, this system offers a more reliable way to test new TB drugs before they reach human trials. It can reduce failures at later stages and help identify effective treatments faster.

 

Comparing Existing Drug Testing Models

Currently, TB drug testing follows three main approaches:

First, drugs are tested directly on free-floating bacteria in laboratory dishes. While simple, this method ignores the role of human immune cells and tissue structure.

Second, mammalian cells grown in 2D plates are infected with TB bacteria. This approach includes host cells but still lacks the complexity of lung tissue.

Third, animal models are used to study disease progression and drug effects. Although useful, animal studies are expensive, slow, and not always predictive of human outcomes.

Recent regulatory changes, such as the US FDA Modernisation Act 3.0 and India’s New Drugs and Clinical Trials Rules, encourage the use of advanced models like 3D organoids and organ-on-a-chip systems. The IISc hydrogel model fits well within this modern framework.

 

Implications for Drug-Resistant TB

India is a global hotspot for drug-resistant TB, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. In 2024 alone, India contributed a significant share of the world’s MDR and rifampicin-resistant TB cases.

The new 3D model opens the door to testing drugs against resistant TB strains using patient-derived bacteria. Researchers believe that by infecting the hydrogel system with clinical isolates of resistant TB, they can identify drugs that work where existing treatments fail.

This is especially important because drug-resistant TB treatment can last up to two years, involves severe side effects, and has lower success rates.

 

Moving Closer to Real Lung Conditions

The IISc team is now working to further improve the model by recreating TB granulomas. Granulomas are dense clusters of immune cells that surround TB bacteria in the lungs. These structures can either contain the infection or allow bacteria to persist and spread.

Granulomas also make drug delivery difficult, as medicines struggle to reach bacteria hidden deep inside. A model that accurately mimics granulomas could provide critical insights into why some treatments succeed while others fail.

Understanding these mechanisms could lead to shorter, more effective TB therapies.

 

Why This Matters for India and the World

India has committed to eliminating TB as a public health problem by 2025, an ambitious goal. Achieving this requires faster diagnosis, better drugs, and more effective research tools.

The IISc 3D lung model represents a shift toward more realistic, human-relevant research. It reduces reliance on animals, improves drug discovery efficiency, and strengthens India’s scientific leadership in global health research.

With sustained funding and collaboration, such innovations could significantly shorten TB treatment timelines and save millions of lives.

 

Conclusion

Tuberculosis is not just a medical challenge but a scientific one. The development of a 3D lung-like TB model by IISc researchers marks a turning point in how the disease can be studied and treated. By closely mimicking human lung conditions, this model bridges the gap between laboratory research and real-world patient outcomes.

As India continues its fight against TB and drug-resistant infections, such cutting-edge research tools could prove decisive. They offer hope for faster drug development, more effective treatments, and ultimately, a TB-free future.

 

UPSC Prelims Question

With reference to the new 3D tuberculosis research model developed in India, consider the following statements:

  1. The model uses a collagen-based hydrogel to mimic the human lung environment.
  2. It has demonstrated drug responses that are often missed in conventional 2D models.
  3. Such 3D models are discouraged under current drug testing regulations in India and the United States.

Which of the statements given above is/are correct?

(a) 1 and 2 only
(b) 2 and 3 only
(c) 1 and 3 only
(d) 1, 2 and 3

 

UPSC Mains Question

“Advanced three-dimensional disease models can transform drug discovery and reduce the burden of infectious diseases.”
Discuss this statement in the context of India’s tuberculosis challenge and recent developments in biomedical research.

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