Many discoveries in science are made serendipitously. But it was curiosity combined with perseverance that helped Dr. Bikul Das from the Departments of Medicine and Pathology, Stanford University to make a landmark discovery of finding the hiding place of dormant TB bacteria in humans. Dr. Das is from the Departments of Medicine and Pathology, Stanford University, and is the lead author of the paper published today (January 31) in the journal Science Translational Medicine. In an email to R. Prasad, he explains the journey that led to the final discovery.
Did you find the dormant TB bacteria in the bone marrow stem cells by chance or did you look for them?
I was in Delhi in 1994 planning to study towards an MD in Medicine, with a future aim to work on oncology and bone marrrow transplantation. But I failed to secure an MD seat and so decided to take a job at Mongar Hospital in Bhutan. The goal was to do self-study and get self-trained. Hence, I did a lot of bone marrow biopsy for patients with fever of unknown origin. In clinics you get patients with chronic fever and it could be due to kala-azar, malaria, TB, leukaemia etc. So a bone marrow biopsy is indicated to make a diagnosis.
Since my goal was to get trained for bone marrow transplantation, I did those biopsies very meticulously. I also looked for TB bugs by doing AFB staining. In those biopsies I saw AFB positive bugs in bone marrow, and occasionally inside progenitor cells. I was not sure if those were stem cells, as a biopsy cannot confirm those cells to be stem cells or progenitor cells.
During that time I was also working on learning more about stem cells, and the idea came to my mind that if TB bugs indeed reside inside bone marrow stem cells, it could explain why it is so difficult to treat TB. At that point of time, I also read a research paper by Toronto’s John Dick on leukemia stem cells. So, I thought that if cancer could hijack stem cells, pathogens might also do the same thing.
In how many people did you see the bacteria in the stem cells?
I don ‘t remember; it was a long time ago. All I remember is that I saw them and showed them to my professor who just laughed at me saying that it was impossible for TB to hide in stem cells because if that was the case, we should see a lot of blood disorder in TB cases. So I stopped doing those staining [work].
Did you at that point realise that they were stem cells that had the dormant TB bacteria?
No I did not realize it. I only made a theoretical construction of my idea that the cells that I saw were stem cells and the bacteria were dormant, because some of the patients did not have active TB.