The 11th of June 1979 was a day clinical pathologist Robin Warren would never forget. It wasn’t just the fact this day was his forty-second birthday and he would be celebrating with his family that evening. No, something he was viewing in the microscope caught his eye which he described as “a funny-looking thin blue line stuck on the surface of the cells in some areas”.
This is a condensed version of an essay on how Dr Robin Warren discovered the cause of stomach ulcers. The unabridged essay, Warren and Marshall – Changemakers, can be downloaded here.
It’s not what you look at that matters, it’s what you see.
— Henry David Thoreau, American essayist
What he did next was to examine this area with a higher powered microscope. He had no idea that by exploring this curiosity further it would change his life forever and would result in him being awarded–together with a colleague–the Nobel Prize some 26 years later. But it wasn’t going to be an easy journey.
The practice of pathology, with the detailed examination of the body, including dissection and inquiry into specific maladies, dates back to ancient times. However, pathology as a formal area of specialty was not fully developed until the late 19th and early 20th centuries. Today there is a range of sub-specialties, and although Robin trained as a general pathologist his ongoing work was mostly in histopathology which involved the microscopic examination of biopsy specimens.
Usually Warren would be looking at tissues using a low power microscope as most things of interest can be seen. On this occasion the biopsy was from a patient suffering severe gastritis —an inflammation of the stomach lining. Being curious as to what it might be, he then used the highest power light microscope he had available to clearly see little organisms – bacteria – growing there.
Warren was well aware that that bacteria could not grow in the stomach since stomachs are acidic. But every so often he might come across something unusual as a once off. Was this one of these occasions? His colleagues finally agreed these bacteria were there but didn’t believe their presence was of any significance.
That day he concluded in his report with the following statement:
These bacteria . . . appear to be actively growing and not a contaminant. I am not sure of the significance of these unusual findings, but further investigation of the patient’s eating habits, gastro-intestinal function and microbiology may be worthwhile.
No one else in his department was interested, so he set out to find out in his own time if this was a common occurrence and what these bacteria doing there in the stomach. And as soon as he started looking he found instances of bacteria being present in around half the biopsies he examined.
Why hadn’t he noticed them before? This was a question he asked himself and was later to find out that the presence of bacteria had been noted over the last 100 years but no one took it further.
Over the next two years he collected more evidence to be able to come up with the conclusion that signs of inflammation were always present in the stomach lining close to where the bacteria were seen. He didn’t believe he had all the proof he needed but since he couldn’t get cooperation from the clinicians to provide the particular biopsies he needed, he couldn’t go any further. He was at the stage of reporting his preliminary findings and was in the process of writing his paper. It seemed that his ability to change the traditional view of how ulcers were formed was doomed to failure.
But then a dramatic change took place. It was the middle of 1981 when Barry Marshall walked into his office. He had just been appointed as the new gastroenterology registrar and as part of his specialist training he was required to write a research paper before he moved on to his next assignment. Warren explained what he had come up with so far, but said later that Dr Marshall “did not seem particularly interested”. However Marshall did agree to take a series of biopsies during the rest of that year showing apparently normal stomachs for Warren to see if the bacteria was present.
This was the breakthrough that Warren needed – he had found a clinician who would provide him with the samples he required to prove his case. Marshall did provide the biopsies during the remainder of the year and became very interested in following through on the study whenever he was able. So much so that two years later Marshall was leading the charge to have their now combined research accepted by the medical community.
Robin Warren had made his major contribution as a change initiator and now it was time for Barry Marshall to become the change master. Eventually both would be recognised as joint winners of the Nobel Prize in Physiology or Medicine in 2005.