Bug of the soil to treat Tuberculosis

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Till the end of the second world war, Tuberculosis (TB) had no cure. Bed-rest, sunlight, and some fresh air were standard TB treatments. While some self-healed themselves, most would die after a long wait. Even Penicllin, famous and marvellous first antibiotic, did not make a dent. First useful medicine against TB, was following footsteps of its predecessor, penicillin. Like penicillin, we sourced it from another microbe, and its discovery also led to a Nobel Prize. However unlike penicillin, it is less celebrated, and features in less than even a handful of postage stamps. We discovered this medicine, from a soil-bug, we know today as “streptomycin”.

Selman Waksman: Discoverer

Born in 1888, Selman Waksman completed high school in Odessa, Ukraine. In 1910 he and his family migrated to America, where he completed graduation from Rutgers in New Jersey, and doctorate from University of California, Berkeley. His doctoral work was on actinomycetes, a bacteria found in soil. In 1918, he was back in Rutgers as a soil microbiologist, a unique designation in those times.

While Waksman continued his research on various types of actinomycetes, real breakthrough came in 1937. His PhD student isolated a substance tyrothricin from a soil bacteria, that inhibited growth of pathogenic bacteria. This was astonishing as soil, we all considered as contaminant, could also kill harmful bacteria. Waksman group’s search for a useful bacterial product, that can be used as an antibiotic was more systematic. He was testing a variety of products, on multitude of bacteria. In 1943, his PhD student Albert Schatz, found another such substance, and this time it was toxic for bacteria, bit not for animals. Streptomycin it was. Soon thereafter, scientists tested this new substance on TB infected guinea-pigs, and started seeing incredible cures.

Streptomycin clinical trials

First human streptomycin-TB trial took place in 1947-48. In this trial, 55 patients got Streptomycin, and another 52 got bed-rest (which was standard of care then). Six months later, 4 died in streptomycin group, and 14 in the bed-rest group. Despite this success, clinical cure was a rare occurrence. In 1950, PAS (another drug that was recently discovered in Sweden) was added to Streptomycin. Cure rates were better.

Two-drug combination was better than either alone. In 1952, a third anti-TB drug INH was added to the regimen, that was used for over two more decades. Despite this success, treatment for TB was still long 24 months. Ethambutol replaced PAS in 1960s, and treatment was 18 months. Rifampicin in 1970s, and Pyrazinamide in 1980s reduced the treatment duration further. Standard 6-month TB treatment in 1990s included Rifampicin, INH, Pyrazinamide and Ethambutol. Streptomycin was fifth drug, to be used in rare instances of treatment default. Today, streptomycin used in selected instances, as less toxic and more effective drugs are now available.

Soil bugs and a plethora of drugs

In 1952, Waksman received Nobel Prize in Medicine. The prize citation read his contribution as “ingenious, systematic and successful studies of soil microbes that led to the discovery of streptomycin.” Indeed, Waksman pioneered study of soil microbes for 24 years, and led a team of PhD students who were focussed on the same theme. Further, Waksman donated most of his prize money, as well as royalty from commercial production of streptomycin, to establish institute of microbiology at Rutgers.

Streptomyces species have given us many a useful products. These include antibiotics, anti-fungal drugs, and even some anti-cancer medicines. List of streptomyces products is rather long. Our struggle against tuberculosis and other infectious diseases is long. Eventually it was one of the bugs, that has led the way to control and even eliminate TB from many countries of the world.