STAT, January 7, 2016
In 1991, a German couple hiking in the Alps came across the body of a middle-aged man lying face down in a snowfield. It took days for a recovery team to hack him out of the ice and haul him by helicopter and truck to a lab in Austria. There, scientists determined the man had died 5,300 years ago.
Ötzi, as the man was nicknamed (after the nearby Ötztal Valley), has kept scientists very busy for the past 24 years. They’ve even built an entire research center — the Institute for Mummies and the Iceman in Bolzano, Italy — to house Ötzi and study him. They’ve slowly extracted one clue after another about how Ötzi died and, more importantly, how he lived.
But Ötzi still has much left to tell us. On Thursday, researchers reported in the journal Science that they have reconstructed the entire genome of a species of bacteria that lived in his stomach. Now Ötzi may be able to tell us not just about ancient humans. He can tell us about ancient microbiomes, too.
Part of the reason Ötzi is so revealing is the way he died. He was probably killed by an arrow to the back. His body was then quickly buried in snow and then freeze-dried. As a result, he wasn’t torn apart by scavengers or decomposed by microbes.
When researchers began to study Ötzi, they focused their attention on his anatomy, using X-rays to probe his bones, muscles, and organs. But in recent years they’ve also begun using DNA-sequencing technology to search for genetic material. In 2012, researchers published Ötzi’s entire genome, which showed he was closely related to people living today in Corsica and Sardinia. He had genes for type O blood and brown eyes; he was probably lactose intolerant and ran an increased risk of coronary heart disease.
While the geneticists were piecing together Ötzi’s genes, the anatomists made a surprising discovery: his stomach. It had migrated up into his rib cage, where it had been hidden from scientific view for 16 years.
After its discovery, Frank Maixner, the coordinator at the Institute for Mummmies and the Iceman, and his colleagues decided to search Ötzi’s stomach for one of its best-known residents: a species of bacteria called Helicobacter pylori.
Helicobacter pylori causes stomach ulcers and gastric cancer. But that doesn’t mean that H. pylori is nothing more than a microscopic enemy of our species. It only causes ulcers and gastric cancer in a small fraction of its hosts; in the rest, it lives harmlessly. Some research even suggests that in children, H. pylori helps the immune system develop properly, reducing their risk of immune disorders like asthma.
Ever since scientists discovered its link to ulcers in the 1980s, they’ve wondered how long H. pylori has been lurking in our ancestors. It might have leaped into our stomachs relatively recently, or it may have been adapting to our bodies for a long time.
In recent years, studies on H. pylori in living people have hinted that it’s an old lodger. The deepest branches of the bacteria’s family tree can be found in Africa, where our species originated 200,000 years ago. As humans expanded to other continents, they took distinctive strains with them.
Maixner and his colleagues decided to test that hypothesis by looking in Ötzi for the bacteria. They carefully extracted bits of his stomach to study.
“The material was quite crumbly — it was like sand,” said Maixner. But to his delight, it was rich in DNA. Some came from Ötzi himself, and some from the animals and plants in the food he ate before he died. And some, it turned out, came from H. pylori.
Whenever scientists find DNA in ancient remains, they have to take extra steps to rule out the possibility that the DNA actually comes from some modern organism that contaminated their equipment.
In their new study, Maixner and his colleagues only found H. pylori DNA in the stomach, and not in nearby tissue. The DNA was also damaged in a distinctive way that allowed them only to see DNA that has been lying around for thousands of years.
“These two facts led us to the assumption that we were on the right track,” said Maixner.
The scientists then pieced together overlapping DNA sequences of Ötzi’s H. pylori. Eventually they could build up almost the entire genome of the microbe. Before the new study, H. pylori expert Martin Blaser, the director of the Human Microbiome Program at New York University Langone Medical Center, had been skeptical that anyone would ever find DNA from ancient H. pylori. “Now we have a solid piece of data,” he said.
As old as Ötzi’s bacteria may be, they were already pretty much the same as ones carried by humans today. They had the same genes that lead H. pylori to cause ulcers and gastric cancer. With Ötzi’s stomach turned to sand, Maizner has no way to see if he had those woes. But he certainly was at risk for them.
Ötzi was also able to shed some light on how H. pylori came to Europe. In living Europeans, H. pylori is an enigmatic chimera. Some parts of its genome closely resemble the DNA of H. pylori carried by people in northeast Africa. Other parts match H. pylori from south Asia. Scientists have long suspected that two strains of the bacteria from these regions must have come together in a single stomach and swapped DNA. But they couldn’t say when or where that exchange took place.
Ötzi, it turns out, had bacteria that were profoundly different from that of living Europeans. “Compared to living Europeans, he has a nearly pure ancestral Asian strain,” said Maixner.
Maixner and Blaser both said that this finding could fit a few different scenarios.
It’s possible that Europeans started out with a strain of H. pylori related to the south Asian strain. At some point after Ötzi died, people arrived in Europe with the northeast African strain, and the two strains combined.
Alternatively, Europeans might have started out with the northeast African strain. Ötzi might have carried a newly arrived strain from south Asia, which had yet to combine with the older one and spread across the continent.
In either case, these strains had to come together with the ancient movement of human populations into Europe. “There had to be an intimate contact of these people,” said Maixner.
But Mark Achtman, a microbiologist at Warwick Medical School in England, doesn’t believe any broad conclusions at all can come from the new study. For one thing, the bacteria come from a single person. “Go get 30 other mummies from around the world and get more data,” he said.
Unfortunately, 5,300-year-old stomachs don’t grow on trees.
For now, Maixner plans to study Ötzi’s bacteria to better understand how Europe’s two strains combined. He’s curious to see how some genes survived in the new chimera while others disappeared. The answer could potentially explain why Europeans suffer fewer complications from H. pylori infections than East Asians, for example.
“It’s not easy to answer big questions immediately,” said Maixner. “We have to start to dig into the data in more detail.”
Copyright 2016 Boston Globe Media. Reprinted with permission.