Bill & Melinda Gates Foundation

Unlocking TB's Mysteries

March 23, 2014

On March 24, 1882, Robert Koch, a German physician and researcher, delivered a lecture that marked the beginning of modern medicine. He told his audience that he had identified a tiny, single-celled organism, Mycobacterium tuberculosis, as the underlying cause of one of humanity’s deadliest diseases. In doing so, Koch revolutionized the scientific study of infectious diseases and paved the way for the development of breakthrough diagnostics, medicines, and vaccines that have transformed life as we know it.

One of the ironies of Koch’s discovery is that the bacterium he identified as the cause of tuberculosis (TB) remains a challenging and elusive foe more than 130 years later. We have applied Koch’s “germ theory of disease” to the global eradication of smallpox and to successful efforts to transform once deadly childhood diseases such as diphtheria, pertussis, measles, mumps, and rubella into rare afflictions that generate sensationalist headlines in the United States and Europe when periodic outbreaks occur among the unvaccinated. But we still have much work to do to bring TB under control.

Recent studies suggest that TB has co-evolved with humans over the past 70,000 years. The bacterium has devised many strategies that allow it to persist in humans, and we still don’t fully understand these mechanisms. Unlocking these mysteries could allow us to develop new tools to control the global epidemic:

  • We need an effective blood test to diagnose people who have developed TB or are likely to do so. Currently, TB patients have to cough up sputum from their lungs, which isn’t an optimal way to diagnose disease.
  • We need better drugs that can deliver a rapid cure. TB is difficult to treat because it embeds itself in tissues that are hard to reach. This means that it still takes 6-9 months to cure a typical case.
  • We need better vaccines that can prevent TB in adults. The current TB vaccine - BCG - can prevent severe disease in babies, but it does not prevent lung disease in adults.

In reality, these are just some of the challenges we face. But as we mark World TB Day in 2014, I am more confident than ever that we can develop the tools we need to beat this age-old disease. The truth is that the discovery and development of antibiotics in the 1930s and 1940s contributed to decades of underinvestment in TB research because antibiotics transformed TB from a disease that killed 1 in 7 people worldwide into a curable condition that virtually disappeared from wealthy countries by the 1960s. We stopped worrying about TB, and we did little to advance TB research as a result.

That trend changed a decade ago when a coalition of government, private-sector, civil society and philanthropic partners agreed to accelerate investment in R&D for new TB tools. By then, the most common treatments for TB had been in use for 50 years, and the rapid emergence of drug-resistant strains of TB had created a potential global health crisis.

The good news is that turnaround in TB R&D investment is starting to yield results. We have two new treatments for TB – bedaquiline and delaminid – and we are making progress in efforts to develop new combination regimens that could treat all strains of TB including drug-resistant strains.

Through the work of the Global Alliance for TB Drug Development and special initiatives like the TB Drug Accelerator and the Critical Path to TB Drug Regimens, scientists are searching the chemical compound libraries of the world’s major drug manufacturers to identify novel molecules that could deliver a rapid cure for TB in combination with other drugs. The desired end product is a treatment that can cure TB in just a few months.

I am also optimistic that we can beat TB because we have new tools and technologies that can help us decipher many of TB’s mysteries For example:

  • We now have the capability to sequence the genes of the TB bacterium.
  • We have increasingly sensitive tools that allow us to analyze how single cells operate.
  • We have insights from decades of path-breaking research on cancer lesions that can help us understand how the growth of tuberculosis lesions can be short-circuited.  

These new research tools and approaches can help us accelerate TB research and produce the new drugs, diagnostics, and vaccines that could ultimately eliminate TB in the next few decades.

But any progress that we make will ultimately depend on effective advocacy led by great organizations such as RESULTS, Treatment Action Group, Doctors without Borders, and the Stop TB Partnership. The efforts of these organizations have been instrumental to revitalizing global investment in TB R&D and creating new tools to fight TB. And you can help stop TB by lending your support to their lifesaving work.

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