History has a way of repeating itself. That is why, when John Aitken suggested I read The Forgotten Plague: How the Battle Against Tuberculosis was Won – and Lost by Frank Ryan, M.D., I jumped at the chance. Indeed, I have not been disappointed. It’s a fascinating book, rich with detail that I have found applicable to the research being conducted now with Crohn’s disease. As you may surmise from my involvement with this site, I am a bit biased in my opinion that a mycobacteria plays a starring role in the development of Crohn’s disease. Therefore, any lessons I can glean from past mycobacterial research is of value. Highlighted below are some passages from the first half of the book that seemed of particular interest. I hope that you will enjoy the brief foray into the history of tuberculosis, and notice some parallels to the fight against Crohn’s disease today.

• In most people, the initial TB infection is fought off by the body. TB has the ability to eat our white cells from the inside, multiplying from inside the white cells themselves. Because our body is unable to digest the waxy coating in the TB cell wall, it surrounds the offending bacteria and walls it off. There is always a bit of living, walled off TB inside an asymptomatic person due to that initial exposure. Relapse, always a possibility, occurs when our physical and mental health is lowest.
• “The cure for the greatest killer in history would not emerge from the great centres of medical learning. No more would it arise from the collective efforts of the tuberculosis experts toiling away in the great sanitoria complexes. Instead it would come from the genius, courage and selfless devotion of a tiny handful of men, often the most unlikely of champions, working alone in disparate countries, yet every one of them gifted in his own unique way.”(1)
• The discovery of Prontosil in 1933 by a German researcher, the first antibiotic to cure streptococcol infections, was revealed to the world in a journal article published in 1935. Millions of people may have immediately benefitted from this miraculous discovery, but instead it was regarded cynically. The book recounts the story of a woman dying from a streptococcal infection in New York, whose family insisted she be given Prontisil. When she recovered, the doctors refused to believe it was Prontisil that was responsible: “Naturally our staff were pleased, but they were particularly pleased because this happy combination of events had occurred in a university hospital, with its high scientific standards…Isn’t it fortunate that this happened here in the New York City Hospital, and not in some small hospital out in the sticks, where they really would have believed this German dye had made her better.”(2)
• Early tuberculosis research included studying earthworms. Although this seems ludicrous, there was a valid theory that something in soil must be able to kill and digest the tuberculosis bacteria (and all other bacteria) or else pathogenic bacteria species would overwhelm the world. One researcher had previously extracted an enzyme from soil capable of destroying the pneumococcus capsule. Since earthworms were able to digest TB and remain unaffected, they must contain an enzyme or substance to kill TB. Although this was not the ultimate solution, it was an interesting tangent worth mentioning.
• Gerhard Domagk, the Nobel prize winning researcher who discovered the antibiotic Prontosil, once wrote about his struggle with TB, “Man must want more than he is able to achieve. No matter that the borders may be drawn in harsh reality very early and very soon. If we do not reach for the stars, the desire to do more than one is physically able to achieve, to want to do more than is humanly possible – all this is often the first step that will lead to modest success.”(3)
• Since Domagk worked in World War II torn Germany, before he could begin work on tuberculosis he was directed to address the wartime disease of gas gangrene. He did this research, publishing his findings in a book giving all military doctors the information they would need to treat this condition. Instead of being gratefully received and the treatment promptly implemented, it was largely ignored. Domagk attempted to advocate for this new drug synthesized by Bayer Pharmaceuticals, and was instead met with criticism and derision. It wasn’t until two years later that he was invited to give a demonstration, proving his research in front of a live audience of surgeons. The establishment believed that gas gangrene was caused not by a bacteria, but by a poison, so cut or amputated the affected region. The pattern of dismissing new science without taking an objective view of the data seems to permeate medical history.
• Eventually, the German portion of the TB research led by Domagk came to a halt due to the war. They simply ran out of space, animals, feed for the animals and lab supplies due to nightly bombing raids and country wide shortages. Most grisly, fewer and fewer workers arrived at the laboratory. Most were wounded, homeless or dead and it was unconscionable to continue work under such conditions with a deadly bacteria. The photo in the book of the crumbling lab during wartime is almost unbelievable, and a testament to Domagk’s perserverance. Important discoveries need not always come from the premier institutions.
• In the United States, two researchers (Feldman and Hinshaw) were simultaneously working on the TB problem. For years they tried hundreds of chemicals and derivatives until they finally found one called Promin that showed some promise. They presented their research in 1942 at the American National Tuberculosis Association annual meeting. “Sadly, they received no encouragement from the audience, and, in fact, the report was received with cynicism, a short-sighted reaction that would become all too familiar to many of the pioneers in the tuberculosis struggle over the next few years.”(4)
• As a post script to the Promin saga, although it did not end up successful for TB therapy due to side effects, it became the first successful treatment for leprosy.

Next up in Part 2 – streptomycin, the cure, how multi-drug resistance happened and what AIDS has to do with it.

(1) Ryan, F. (1993). The forgotten plague: How the battle against tuberculosis was won–and lost. Boston: Little, Brown. 31-32.
(2) Ryan, F. (1993). The forgotten plague: How the battle against tuberculosis was won–and lost. Boston: Little, Brown.102-103.
(3) Ryan, F. (1993). The forgotten plague: How the battle against tuberculosis was won–and lost. Boston: Little, Brown. p.89.
(4) Ryan, F. (1993). The forgotten plague: How the battle against tuberculosis was won–and lost. Boston: Little, Brown. p. 227.