Helicobacter (3): A Reckless Toast
The two internal medicine residents scanned their respective auditoriums. Two physicians separated by an ocean, and two hospitals.
"Good afternoon, colleagues of Royal Perth Hospital. Internal medicine resident, Marshall."
"Hello, physicians of Stanford Hospital. Internal medicine physician, Parks."
"Peptic ulcers are caused by bacteria."
"And today, I—"
Marshall lifted a small beaker filled with a murky liquid, as though proposing a toast.
"—will drink this culture teeming with bacteria extracted from the ulcerated tissue of a peptic ulcer patient."
"Through a thought experiment designing a bacterium theoretically capable of inducing peptic ulcers—"
Amid the bewildered expressions of the senior physicians—
"Dr. Marshall, what exactly are you—"
Before the audience could react, Marshall downed the entire contents of the bacteria-laden beaker in one gulp. The taste must have been dreadful. Naturally.
Barry Marshall wiped his mouth.
"I will prove it."
"Let us begin the presentation."
A brief silence fell over both auditoriums. Among the sea of physicians, an unspoken question hung in the air, as clear as if spoken aloud.
What on earth is he talking about?
***
A bombshell statement. In the original history, some physician had swallowed a bacterial culture. I had no intention of doing the same. This was a disease that could lead to stomach cancer, after all. As I had said repeatedly, peptic ulcers were never to be taken lightly. It was a dangerous condition.
I surveyed the internal medicine seminar room. As expected, the eyes staring back at me were not ones that would easily accept my words. The dogma that no bacteria could survive in stomach acid had held for a full century. Overturning a century of tradition would require irrefutable evidence.
The Spider-Man principle applied to research as well. With great power came great responsibility, and with a bold claim came the need for bold proof. In the past, they would have already begun dissecting my argument. Perhaps my accumulated reputation was the only reason they were still listening.
"Yes. After studying gastric lesion tissue from peptic ulcer patients for one week—"
"One week?"
The dean, seated in the front row, let out a visible sigh. His lips moved in a quiet mutter: This kid again.
"Yes."
"Continue, then."
I nodded and pressed on.
"Yes. The thought experiment goes like this. If we were to create a bacterium that causes peptic ulcers, how would we do it?"
The gastroenterology professor in the front row looked at me, his expression clearly asking whether such a thing was even possible. Professor Michael Fogel. A senior figure in gastroenterology. He had spent his entire life learning and teaching that peptic ulcers were caused by stress. His skepticism was understandable. Still, he would change his mind once he heard the rest.
In any case, the senior professor raised his hand and spoke.
"Stomach acid has a pH of around 2. The acidity is so strong that bacteria cannot survive there. Dr. Parks, your courage is admirable, but there is a reason no one has found the cause of peptic ulcers."
I nodded.
"A fair point. But can human cells survive in a pH 2 environment?"
They could not. Bacteria capable of growing in a pH 2 environment were extremely rare. Helicobacter pylori itself could not survive in such strongly acidic conditions. It merely sought out less acidic niches within the stomach.
The gastroenterology professor continued.
"That is because of the protective mucus layer secreted by the gastric mucosa."
Exactly.
"Yes. So then, if a bacterium existed that could penetrate the mucosal layer, it would mean survival in the stomach is not impossible."
"Hmm… The mucosal layer exists precisely to block bacterial movement and proliferation."
"That is also true. However, we already know of another bacterium specialized in penetrating mucosal layers. A much older one."
I waited for a response, but none came immediately. The infectious disease professor, who had been studying me intently, finally spoke.
"Syphilis?"
"Yes, syphilis. Do you know what Treponema pallidum looks like?"
"Long and slender, I suppose."
Even an infectious disease professor did not have every bacterium's morphology memorized.
"It is spiral-shaped. Its screw-like form converts rotational motion into linear motion, allowing it to burrow through mucosa."
Professor Fogel folded his arms.
"So. Are you saying you found spiral-shaped bacteria in the peptic ulcer tissue this time?"
Precisely.
"Please take a look at this."
I showed Professor Fogel the journal I had brought from the reading room. A journal discolored by decades. The moment he saw the bundle of papers, he gave me an incredulous look. Research papers were not museum exhibits. They were meant to be read.
"What… This is a paper written in Polish in the 19th century. Where on earth did you find this? Can you even read Polish?"
"For the sake of the patients."
At those words, the seminar room fell silent. Large hospitals usually kept interpreters on standby. What those people did when there was no interpreting work, I had no idea.
"Then look at Figure 1."
"What is it?"
Naturally, it was a hand-drawn illustration of spiral bacteria by a Polish physician from the 19th century.
The gastroenterology professor pressed his temples.
"Look at the paper I brought. It is a 1899 paper written by Dr. Jaworski. It details the discovery of spiral-shaped bacteria in the human gastric mucosa."
A murmur rippled through the room. The physicians present hurriedly passed around the seventy-nine-year-old journal, unable to believe what they were hearing. At their age, this was practically elder abuse.
That cannot be right. Not this guy again?
After several minutes of confusion, the head of infectious diseases, Professor Kenneth Bosti, raised his hand with a question.
"Yes."
"But… according to your theory, why do you think this bacterium was discovered yet its significance went unrecognized for nearly a century?"
"Because of the Gram staining process. Physicians almost always try to observe bacteria through Gram staining, do they not? Both the 19th-century Polish physician and I used silver staining."
"Silver staining, you say."
"Syphilis also requires silver staining to be visible. Similar function means similar structure, and similar structure means similar detection methods."
In summary: Helicobacter pylori was drill-shaped and burrowed into the gastric mucosa to cause peptic ulcers. The syphilis bacterium was likewise drill-shaped, burrowing into genital mucosa to cause genital ulcers. The same principle.
"Ah…"
The infectious disease professor nodded. The seminar room was still filled with physicians muttering among themselves. If what he says is true, could this bacterium really be causing peptic ulcers?
Looking back, it was a remarkably simple story.
Professor Fogel looked at me again.
"But do you have evidence that this bacterium causes peptic ulcer symptoms? Separate from merely being able to grow in the stomach."
Someone simply needed to drink the bacterium to find out immediately. Though there was a better way.
I opened my mouth.
"I believe it is similar to syphilis. It is highly likely to be treatable with antibiotics. And if peptic ulcers resolve with antibiotics…"
"That would prove it is the cause."
"Yes."
Professor Fogel frowned. But by this point, he seemed to have run out of counterarguments.
"It appears you are correct."
I continued.
"Thank you. Returning to clinical application, I believe peptic ulcers can be treated by administering antibiotics along with several other medications."
The audience wore expressions of shock. After all, physicians conducted research ultimately to treat patients. The goal was to deliver new treatments as quickly as possible. They could never have imagined it. The 1970s. The era after the moon landing. Even in this age, a single internal medicine resident had used a century-old book, an optical microscope, and century-old staining reagents to catch the hidden culprit that had evaded physicians for a hundred years. It was only natural that it was difficult to believe.
***
Barry Marshall lay in a hospital bed. As expected, one week after drinking the bacterial culture, he had developed a peptic ulcer. More precisely, severe gastritis at the pre-ulcer stage.
"Professor… My stomach feels strange."
Royal Perth Hospital. Dr. Warren scratched his head, his expression asking what Marshall had expected. Well, it would have been stranger if he had felt nothing after drinking a culture of bacteria that caused peptic ulcers. It was fortunate that no serious aftereffects remained.
"There is a reason other physicians do not conduct human experiments. There are plenty of patients, but most cases involve bacteria ingested with food. What on earth were you thinking, culturing it and swallowing it?"
"I wanted to prove it."
Dr. Warren showed him the black-and-white photograph taken during the gastroscopy. An image of the gastric mucosa, devastated like the surface of the moon. Irrefutable evidence for the hypothesis.
"In all my years as a physician, I have never seen gastritis this severe. No one in human history has ever drunk pure peptic ulcer fluid. Why did you do it?"
It was not as though he had no plan.
"While culturing the bacteria, I also ran antibiotic susceptibility tests. I thought that once I proved it, I could just take antibiotics and recover."
"Since you have proven it, take the antibiotics quickly."
Marshall nodded.
"Once I have time, I should visit Stanford. I want to meet the physician who proposed the peptic ulcer research this time and discuss it…"
The physician who had agreed to research peptic ulcers together. I should at least see his face. I was curious what kind of person he was.
"Very well. Go once your ulcer has healed."