So, what’s a young physician to do when he’s growing tired of being ignored or dismissed? What can you do if both the medical orthodoxy and Big Pharma are trying to sweep your ideas under the rug? Dr. Marshall drank a foamy brown broth full of the microbe H. pylori extracted from one of his ill patients and hoped that it would make him sick.
And it did. At first, Dr. Marshall experienced some minor stomach discomfort, but by day five he was vomiting, and by day ten his stomach was inflamed, completely colonized by H. pylori. Inflammation and gastritis took hold of his body from the H. pylori infection, and he was well on his way to developing a full-blown ulcer. His wife, Adrienne, stepped in and convinced him that it was time to cure himself with antibiotics.
The antibiotics eradicated the H. pylori in Dr. Marshall’s stomach, and he made a full recovery. But despite the additional experimental evidence supporting his theory, many clinicians at the time remained unconvinced. It took almost another ten years of scientific advocacy before clinicians began to take the theory seriously. Marshall and Warren not only went on to convince the world of the veracity of their theory but also were awarded the Nobel Prize in Physiology or Medicine in 2005 for their groundbreaking discovery.
Lucky for Dr. Marshall, he didn’t try to infect his wife, Adrienne, with H. pylori. Millions of people around the world might still be suffering needlessly today if she had volunteered for this experiment, and he wouldn’t have a Nobel Prize to celebrate. If she—or any other genetic female, for that matter—had drunk the broth instead, his experiment could have failed.
We’ve known for a very long while that ulcers were up to four times more common in men, though we didn’t know why. But now, there is no doubt that it’s because males don’t have the same ability to appropriately fight off microbes, such as viruses and bacteria, that females do. Males are not only incapable of mounting the same vigorous immunological response against microbes as genetic females, but they are also more likely to get gastritis, peptic ulcers, and even gastric cancer as a result of them.
Recent research indicates that the differential responses men and women have to being infected with H. pylori may be mediated through hormones such as estrogens. In fact, giving male mice a type of estrogen called estradiol reduced the severity of gastric lesions caused by H. pylori. In humans, treating cell lines of human gastric adenocarcinoma (otherwise known as stomach cancer) with estradiol, for example, seems to inhibit their growth. So it may not be H. pylori alone that’s the sole reason more men get cancer from being infected. Genetic females are just more resilient than men in dealing with the stress of the infection.
Differences in the level of the sex hormones such as estrogens and testosterone in our bodies are dictated by the chromosomes we inherit. The gonads that produce the sex hormones, such as the testes and ovaries, were formed depending on which sex chromosomes you have. If you’ve inherited a Y chromosome and your gonads are testes, then you’ll have more testosterone than estrogens in your body. Without the Y, there will be more estrogens within your blood. Some female resilience is the result of sex hormones while other female resilience has to do with female chromosomal diversity, cooperation, and of course subsequent superiority as a result of having more than one X chromosome to choose from.
When it comes to resilience—overcoming life’s trials and tribulations—genetic options help women confront one of the biggest challenges of all: not to be consumed by pathogens like the one Barry Marshall and Robin Warren discovered causes peptic ulcers.
The trillions of microbes in our environment are always on the lookout for an easy target, which is why every higher-order organism—be it an oak tree, a French bulldog, or a human being—has some type of immunological defense system. Skin and digestive antimicrobial enzymes provide important barriers that reduce the chance of entry or colonization by pathogens. But what happens when a physical barrier isn’t enough?
Cue the immune system. It evolved to deal not only with pathogenic and cancerous rogue cells but also with parasites such as intestinal worms. The immune system isn’t a distinct organ, like a heart or brain. And that’s a good thing, because it needs to be active both spatially and temporally—everywhere, at any time, all the time.
When it comes to the overall differences between men and women and their ability to fight a multitude of microbial infections, the clinical outcomes are striking. Whether it is bacteria such as Staphylococcus aureus; or Treponema pallidum, which causes syphilis; or Vibrio vulnificus, which causes vibriosis, women are consistently better at fighting these infectious microbes.
Without a strong immune system, you might find yourself with an H. pylori infection you can’t fight off, or something far deadlier. And it’s not just bacteria that females are better at fighting off. It’s viruses as well.
* * *
THE RAIN WAS DEAFENING and I could see the water levels starting to rise outside my window at the Tarn Nam Jai Orphanage. Eventually the entire street was flooded, and the children were cut off from the rest of the city.
There’s a reason that Bangkok used to be called the Venice of the East. Long before all the canals were paved over, they were used to effectively transport people, animals, and goods. But on days like this one, in the middle of the rainy season of 1997, it was as though the past became present, and when the city began to flood, its side streets were submerged once more.
As the water levels continued to rise, I didn’t have much time to reflect on Bangkok’s past glory. There were a dozen children to tend to, some of whom were HIV positive. When your immune system has been decimated by a virus whose evolutionary strategy evolved to do just that, you need all the medical help you can get.
The problem with flooding is often not just the water but also what it carries with it. I noticed a nervous rat running in circles on a small wooden plank floating along the street. It was a sign that the sewers were mixing with what was quickly becoming a river in front of the orphanage. For the six children at Tarn Nam Jai who were HIV positive, exposure to a greater microbial load than normal was a serious danger, because HIV preferentially infects and kills immune cells. Even a simple skin infection can quickly turn deadly in those infected with HIV.
A neighbor was almost cheerfully paddling an inflatable dinghy up and down the flooded streets, rescuing people trapped by the rising waters. Like this local man, the people I met during my time in Thailand were extremely resourceful and independent, characteristics that were often coupled with a reverence for the concept they call sanuk, which loosely translates to “fun”—if it’s not sanuk, it’s simply not worth doing. It’s also a coping mechanism for handling life’s worst moments, like when your street and house are flooding. I learned a lot about sanuk firsthand that summer, and I saw how it helped people get through terrible circumstances, like caring for sick children.
The orphanage was a seventy-five-year-old teak structure that had recently been refurbished. It was surrounded by a lush garden with a pond, and the constant loud calls of birds made it easy to forget at times that we were living in the middle of a busy urban landscape. Housed within its walls were children who were the youngest victims of a growing epidemic that was starting to take a serious toll on the Thai population.
All the children at Tarn Nam Jai were born to mothers who were HIV positive. At that time in the mid-1990s, many children were still becoming infected while in the womb. Transmission of HIV during an uncomplicated pregnancy was around 50 percent then, and that statistic was reflected in the children at the orphanage. (Recently, the Thai government has made immense strides in practically eliminating the mother-to-child transmission of HIV, and it’s the first Asian country to do so.)