by John Aitken
In the olden days we had the rack–now we have the press.
Louis Pasteur, the great French scientist, introduced bacteriology as a branch of science. Pasteur made many great contributions to the study of bacteriology, including demonstrating that bacteria could be cultivated, and that they could also be killed (pasteurization). Like Robert Koch, Pasteur was exploring a new world, and in doing so laid out the principles of fermentation and vaccination. One of Pasteur’s great contributions to the world, and there were many, was the discovery of a rabies vaccine. Pasteur believed passionately in the value of an experiment. One experiment leads to many experiments. Each experiment adds to the knowledge of the experimenter, and this is true in bacteriology, as in any other discipline. Richard Feynman, the famous American Physicist and Nobel Laureate encapsulated the value of investigation in three words: “Do the experiment.”
Experiments have two primary outcomes, either confirmation or rejection. There is, however, a third outcome – The Unexpected. Most publications in medical journals project confidence in the results of the published observations, radiating a secure faith in the value of scientific investigation. This logical account of great labor represents the finished product. There is an old saying, “Success has many authors, and failure only one.” A groundbreaking paper will feature many authors, all keen to get on the paper, while a less momentous publication will only show a few authors. My CV is well populated with the latter.
The process of discovery is somewhat different. If the paper signals a quantum shift in scientific understanding, you can bet that the birth has been difficult. There will have been mistakes, misunderstandings, sleepless nights, multiple failed experiments, and a single shaft of illumination, gradually gaining in intensity. With a lot of luck, that beam of light guides the researcher to a conclusion. Luck is an important ingredient, and don’t let anyone tell you otherwise. Emily Bronte once wrote, “Depend on it, a lucky guess is never merely luck–there is always talent in it too.”
Luck never actually appears in publications as a contributing factor. The lucky observation is the catalyst. Some of the most significant discoveries made in microbiology were flukes of luck. The trick was responding to the chance observation. Sir Alexander Fleming, on first observing the mould that produced penicillin, did not run out of the laboratory shrieking, “I’ve done it!” His actual comment was, “That’s funny.” Fifteen years later we had penicillin, just in time for the beaches of Normandy. Streptomycin, the first antibiotic to work against tuberculosis, was initially cultured from the throat of a sick chicken. It was coincidence that it happened to be discovered in the same facility that was searching for a tuberculosis cure. The mould ended up being put into a screening program to find an antibiotic against tuberculosis. Readers will note that the chicken came first.
Research into Crohn’s disease and Mycobacterial triggers is a fairly solitary occupation and I am not sure what motivates my colleagues. In my case, it is complex. In the early 1970’s, as a result of a trivial complaint, I was given a barium enema. I had commenced training as a medical laboratory scientist, so I knew the basic drill. Not a pleasant experience, and few were interested in my subsequent anecdotes on the procedure. The result, however was no laughing matter. I was told the bad news by telephone that I had Crohn’s disease. In those distant days it was poorly understood, and I was informed that I would eventually have a resection, among other equally bleak predictions. In 1973, “old school” surgeons were not familiar with the term “bedside manner.” Prognosis was straight and to the point.
I spent three years under the cloud of the diagnosis. My colon remained intact and life went on. I eventually asked for a repeat examination and my barium enema came back normal. The original diagnosis had been medical error! Working in a medical lab, I was not unfamiliar with this concept. Mistakes happen. Life went on. The experience changed me in subtle ways, however. I became aware of my own mortality, and this stayed with me, making me a better scientist I believe. I also developed an interest in Crohn’s disease. Whenever a journal came into view, I read the articles on Crohn’s disease with some insight. I read a lot of journals!
As fate would have it, I also inherited a tuberculosis laboratory as part of my job, which was running a microbiology laboratory in a hospital with an academically active Department of Respiratory Medicine. The daily routine in the laboratory consisted of eyeballing the sample cultures and making decisions on the pathogens. Every day was an experiment. I became familiar with seeing “new” organisms and unusual infections. The tuberculosis work was less challenging. Tuberculosis numbers were dropping yearly and the main role was training lab scientists in the techniques. The academics in Respiratory Medicine drew me into a research role, and I started writing papers and contributing to novel research projects. The idea that Tuberculosis-like organisms had a role in Crohn’s disease had been around for a long time, and I was keeping up on the Crohn’s articles. It seemed a small step to start carrying out experiments. I carried out many experiments on many odd organisms, as Crohn’s disease hovered in my peripheral vision.
Sometimes, trial and error leads to a point where the experiments narrow down. This can happen when you get lucky. I think it happened to me. My work now consists in exploring the results of an experiment that opened a door in my head. This happened because I followed the same principles laid out in the 19th century. I had been well trained, and that training was instrumental in recognizing the significance of the observation.
Microbiologists share a common heritage. The techniques we use have been tried and found to be reliable. We try to see the organism with a microscope, and we attempt to culture it. Once culture is successful we identify the organism–then we work out how it kill it. Luck plays an important role in the advancement of medical science, as does study and good training. Louis Pasteur is not so far away from us as we would like to think. That great bacteriologist put it very succinctly: “Chance favors the prepared mind.”