• Martin Laurence

A cautionary tale

In 1981, a young Australian doctor named Barry Marshall used a microscope to detect Helicobacter pylori in stomach biopsies of gastric ulcer patients. We now know that this bacterium causes most stomach ulcers, and a simple round of antibiotics cures patients—at the time medicine was oblivious to this fact. Two very well written accounts of this story can be found here and here, including such gems as:

“Guinea-pig doctor discovers new cure for ulcers”
“They were talking about this terrible person that they imported from Australia to speak,” Marshall told me. “You know: ‘How could they put such rubbish in the conference?’”
“Reader’s Digest and the National Enquirer covered it. Our credibility might have dropped a bit, but interest in our work built.”

Helicobacter pylori's ecological niche is the extremely acidic environment of the stomach, and it had been colonizing this organ in most people since the dawn of humanity. Prior to Marshall’s work, it was widely believed that nothing could grow in the stomach, so an infectious cause for stomach ulcers was excluded outright, without thoroughly checking.

Initially, Marshall’s research was not well received. How could a junior Australian doctor discover something so important, using such simple methods? If this were true, someone else would have figured it out long ago! Here is an old joke along the same lines:

The young economist looks down and sees a $20 banknote on the sidewalk and says, “Hey look a twenty-dollar bill!”
Without even looking, his older and wiser colleague replies, “Nonsense, if there had been a twenty-dollar bill lying on the street, someone would have already picked it up by now.”

Helicobacter pylori does not grow well in culture. Doctors thought the stomach was sterile. They had a flawed theory that ulcers were caused by stress, which they supported with weak animal models and anecdotal evidence. These ulcers could be managed—but not cured—by antacids and similar drugs. The stomach ulcer problem was sufficiently solved for doctor’s taste. However, a subset of patients still needed surgery—and in some cases their entire stomach needed to be removed! They typically had to take drugs for the rest their lives.

Marshall was given a hard time by the medical establishment. He speculated that this was in part because the treatment he proposed cured patients, which meant a major loss of revenue for doctors and pharmaceutical companies. His work was ignored for more than a decade, during which time millions of patients suffered from stomach ulcers, and thousands even bled to death! The cure was sitting on pharmacies’ shelves the entire time.

Barry Marshall faced the same problem as Billy Beane, who introduced sabermetrics to baseball:

"I know you’ve taken it in the teeth out there, but the first guy through the wall, he always gets bloody. Always. It’s the threat of not just the way of doing business, but in their minds, it’s threatening the game. But really what it’s threatening is their livelihoods. It’s threatening their jobs. It’s threatening the way that they do things.
And every time that happens, whether it’s the government or a way of doing business or whatever it is, the people who are holding the reins, have their hands on the switch, they go batshit crazy. I mean, anybody who’s not tearing down their team right now and rebuilding it using your model, they’re dinosaurs." -Boston Red Sox owner John Henry speaking to Billy Bean in Moneyball

What can we learn for Marshall’s work with Helicobacter pylori?

  1. Important discoveries can be missed for decades because of blind-spots in medical research.

  2. Technology needed to make such discoveries can be trivial, enabling researchers with the right approach to solve seemingly intractable problems on a shoestring.

  3. Change is hard! Even with conclusive evidence, Marshall’s work was ignored for over a decade.

The Malassezia Project has many similarities with Marshall’s work. Malassezia don’t grow well in culture. They are small and hard to see using routine histology. They are hard to detect using consensus PCR—worse, most studies which use this technique ignore the fungal part of the microbiome entirely! It was not realized until a few years ago that Malassezia are present inside our bodies, including in our guts. Had their presence been known in 1988, Main and colleagues would have tested antibodies against Malassezia in addition to Candida in their follow-up study (McKenzie et al 1990), likely accelerating a cure for Crohn’s disease by 30 years.

Marshall’s story ended well: he made a website to spread the news that antibiotics could cure stomach ulcers (much like this site), eventually the NIH/FDA accepted his work, and millions of patients were cured using cheap antibiotics. He won a Nobel prize for this in 2005.

It’s crushing that the Helicobacter pylori story did not unfold faster. This would have saved hundreds of thousands of lives and much suffering. In fact, it could have unfolded 30 years earlier, following the work of a Greek doctor named John Lykoudis. In the early 1960s, he patented an antibiotic cocktail called “Elgaco”, which cleared Helicobacter pylori and cured stomach ulcers. He successfully treated thousands of patients at his clinic, but could not get the word out. His work was ignored by the medical establishment, and starting a website would not be possible for another 35 years! He died in 1980. It's tragic.

How do you think The Malassezia Project will end?

#malassezia #hpylori #elgaco


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