Serendipity has always been a vital component of science. Alexander Fleming discovered penicillin, humankind’s greatest antibiotic, as a deadly mould killing a Petri dish full of bacteria that he absent-mindedly left in the open. Viagra was being tried as a possible angina cure when tests on men revealed unexpected side effects.
At one of the world’s premier tuberculosis research laboratories, chance similarly played out its hand. Tinkering with isoniazid to probe how resistance was forming to this frontline anti-TB drug, a team of researchers at the Albert Einstein College of Medicine in New York recently found that dowdy old vitamin C can stop drug-resistant TB.
The findings, published online in the journal Nature Communications last week, suggest a new course for anti-TB drug research and hold out the possibility of shortening treatment by adding vitamin C to existing drugs. The development is at a premilinary stage, as the lead investigator of the study, William Jacobs Jr, acknowledged in an email interview. “It provides new insight to our quest to kill persisters, which is the biggest problem for TB control,” said Jacobs. “But until a human clinical trial is done, we would not really know if it works.”
Yet, every suggestion helps at a time when virtually untreatable strains of TB are spreading across the world. “The big problem with TB control is that a short course of antibiotics is six months long; if you have drug-resistant MTB (Mycobacterium tuberculosis, the bacillus that causes TB), it’s a minimum of two years,” said Jacobs. “We asked why?”
Isoniazid can quickly kill up to 99.9% of TB bacteria in the first few days. But the 0.1% that persist (the “persisters” that Jacobs refers to) gain resistance and require patients to take four drugs over six months. The most evolved strains of TB are now resistant to all the 10 drugs used against the disease. This is not a surprise because TB is one of the most persistent diseases known, an exemplar, as it were, of the wonders of evolution.
The TB bacterium emerged from the planet’s soil. It is a marvel of natural selection, a cocktail of proteins protected by a waxy shell. Over eons it triumphed over weaker strains, and about 40,000 years ago, it found a host: Humans. In the last 200 years, TB has killed more than a billion people. TB now kills nearly 2 million people every year, especially in Africa and Asia, and infects a third of humanity. It particularly targets those with reduced immunity, such as HIV patients.
Allow the TB bacterium a foot in the door and it will launch a new invasion. This is what happens with a missed dose here or an efficacy of 99.9% there. It’s the crack through which TB seeks to evolve, mutate and keep at our throats—quite literally, since that is where the blood it hacks out from the cells in our lungs accumulates.
For 20 years, Jacobs and his colleagues have worked on isoniazid and isolated a new class of mutations that keeps the TB bacterium ahead of science. This time, they sifted through the TB genes that conferred resistance and isolated the amino acid—a building block of life—that deactivated isoniazid. In a test tube, they combined this amino acid, cysteine, with the drug. “To our amazement, instead of conferring resistance, the addition of the cysteine led to the complete sterilization of the drug-treated cells,” said Jacobs, a professor of microbiology, immunology and genetics.
The chemical soup created free radicals, a species of highly reactive molecules, which killed TB. When the researchers later added vitamin C to isoniazid, the result was the same. And since chance had buttressed their long, painstaking research, they took another gamble and used just vitamin C. It killed the hitherto drug-resistant TB bacteria, both multi-drug resistant (MDR-TB) and extensively drug resistant (XDR-TB) strains. When Catherine Vicheze, one of the investigators, brought the results to Jacobs’ attention, he was almost disbelieving of the results.
Would it work for what is called TDR (totally drug resistant) or XXDR (extremely extensively drug resistant) TB, the deadliest strain yet reported, particularly in India? “I am quite confident it would,” said Jacobs.
As researchers explore these frontiers, does it make sense to simply consume more vitamin C, a safe nutrient found plentifully in oranges, lemons, papaya and a variety of fruits and vegetables? It’s hard to conclude that without further research. But two years ago an international research team found that vitamin D—vital to build your bones—played a key role in fighting infections such as TB. It was a confirmation of what was instinct for many centuries: Placing TB sanatoria in sun-drenched areas. No one knew why, but it helped.
What appears to be common sense today could indeed become a cure tomorrow, but not always, and definitely not before scientific research and validation. Serendipity is but a start.
Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology. Comments are welcome at firstname.lastname@example.org. To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail