Published: Jan 3, 2014 | Updated: Jan 5, 2014
By Todd Neale, Senior Staff Writer, MedPage Today
Looking for atherosclerosis in mummies brings the thrill of scientific discovery, but getting access to the "patients" can prove difficult.
In the Horus study, an international group of researchers performs whole-body CT scans on mummies, looking for evidence of arterial calcification. The study was inspired by a trip to the Egyptian National Museum of Antiquities in Cairo, where a descriptive plate claims one of the pharaohs died of atherosclerosis.
But permission to image mummies isn't always easy to come by because of political issues, according to one of the principal investigators of the study, Gregory Thomas, MD, MPH, medical director of the MemorialCare Heart & Vascular Institute at Long Beach Memorial Medical Center in California.
So far, the team has reported results from a total of 137 mummies up to 4,000 years old from four ancient populations of Egyptians, Peruvians, Ancestral Puebloans of the U.S. Southwest, and Unangans from the Aleutian Islands (present-day Alaska). Scans revealed high rates of calcification.
The findings suggest that humans may be genetically predisposed to atherosclerosis, that the disease cannot be explained away as a consequence of modern sedentary lifestyles and poor eating habits, and that there might be risk factors that have not yet been identified. The researchers plan on imaging even more mummies from cultures across the globe in the hopes of gaining insight into what those factors might be.
The "prize mummies" used in the study come from Egypt, Thomas told MedPage Today, but the researchers have been essentially locked out of the country since early 2011 because of political instability.
That January, he and the rest of the team were on their way to Egypt -- which was already becoming unstable -- for what would have been the third expedition to image mummies. They landed in London, but their connecting flight to Cairo was canceled when protests marking the beginning of the Egyptian Revolution flared up. They have yet to return to the country.
Since the revolution, which displaced the government of President Hosni Mubarak, the political situation has been in flux, making it difficult to 0btain permission to continue imaging mummies. The authority that oversees mummies in the country -- the Supreme Council of Antiquities (now officially called the Ministry of State for Antiquities) -- has been subject to the same uncertainty as the larger Egyptian government, and its leaders at any given time are hesitant to make decisions because of it. Plus, anthropological or medical projects are not a high priority, Thomas said.
The difficulty in getting access to Egyptian mummies has encouraged the research team to branch out to other parts of the world, Thomas said, but mummies outside of Egypt tend not be as well preserved.
That's because the Egyptians used an extensive, "artificial" mummification process that could take 70 days and involved removal of many of the body's organs and application of natron (sodium carbonate) to dehydrate and preserve the body. In other parts of the world -- generally with either very cold or very dry climates that discouraged bacterial decomposition -- cultures used a "natural" mummification process that did not involve organ removal or the use of natron.
What Are They Looking For?
The CT scans of the mummies are revealing, in many cases, calcification believed to be indicative of atherosclerosis. Although there is no pathologic evidence that it is, in fact, vascular disease, the researchers don't think it can be anything else, Thomas said.
Looking just at the Egyptian mummies, there was a possibility that the calcification was indicative of the natron used in the mummification process. But when similar calcification was seen in mummies from the other cultures -- which did not use natron -- that possibility was scrapped.
Further support for the presence of atherosclerosis came from the fact that the calcifications were occurring where atherosclerotic calcifications in modern humans tend to occur -- at high-velocity points in the vasculature, Thomas said.
Working under the assumption that the calcification is evidence of atherosclerosis, many on the research team believe that it indicates an inherent, genetic susceptibility to atherosclerosis among humans, albeit one that can be worsened by environmental factors, like diet.
"I still believe that if you follow a low-fat, low-cholesterol diet and avoid what are traditional risk factors, that we can delay atherosclerosis," Thomas said.
He added, however, that the fact that atherosclerosis was prevalent among these ancient cultures -- in which one would expect low cholesterol levels, a relatively healthy diet, an active lifestyle, and a lack of cigarette smoking -- suggests that one or more major risk factors have not yet been established. Researchers have only minimally increased understanding of key atherosclerosis risk factors over the past half-century, he noted.
"It's sobering that we don't understand atherosclerosis as well as we thought we did," he said.
Unidentified Risk Factors
One possibility to explain the presence of atherosclerosis in these populations is inflammation from infection, which was common in ancient cultures. Thomas pointed to an extensive autopsy that was performed about 40 years ago on a teenage boy named Nakht who died around 1,150 B.C. in Thebes (in what is now Luxor) in Egypt. When the boy died, he had four parasites -- malaria, schistosomiasis, tapeworm, and trichinosis.
According to Thomas, a member of the research team -- David Michalik, DO, a pediatric infectious disease specialist at Miller Children's Hospital in Long Beach -- said he's never knowingly seen a patient with four parasites. That would seem to indicate that the infection and inflammatory burden was higher in ancient cultures -- which didn't have antibiotics or an modern appreciation for hygiene -- than it is today.
"I'm suspicious that these ancient people had an inflammatory burden similar to patients with current chronic inflammatory disease," Thomas said, noting that patients with rheumatoid arthritis or systemic lupus erythematosus develop atherosclerosis decades earlier than normal. "And so it may be that if your inflammatory system is revved up that you're going to have a revved up atherosclerosis environment as well."
Another possibility is smoke inhalation from fires used for heat and cooking, Thomas said. He added that he suspects that in the coming decades there will be a greater understanding of the missing risk factors that can explain the presence of atherosclerosis in ancient populations, as well as in modern-day people who have no apparent risk factors.
The Horus study may or may not help identify some of those missing factors; Thomas said that more likely the research will stimulate studies from other groups looking for the unknown factors.
What's Next for the Horus Study?
Thomas said that the research team plans to publish results roughly every 2 years, rather than gradually releasing data. The first data were presented at the 2009 meeting of the American Heart Association and published in the Journal of the American Medical Association. That was followed up by a presentation at the 2011 meeting of the American College of Cardiology (with publication in JACC: Cardiovascular Imaging) and another at the 2013 ACC meeting (with publication in The Lancet).
Thomas said the next round of results may be ready for the AHA meeting in the fall but would most likely come early in 2015.
The plan is to continue imaging mummies from around the world to explore similarities and differences in genetics and environment between the various cultures. So far, the researchers have scanned 180 mummies (and reported the results from 137), and Thomas said that number might rise to about 250 within the next few years.
Ideally, Thomas said, the researchers will be able to find a population that did not have atherosclerosis, but they've come up empty so far. Hunter-gatherer populations without domesticated animals could possibly be atherosclerosis-free, although of the only five hunter-gatherers scanned so far (the Unangans), three -- including a middle-age woman with two-vessel disease -- had calcification.
"We as physicians and lay people have an optimistic belief that if we go back to nature, so to speak, that we'll be okay. We haven't found that to be the case yet," Thomas said, noting, however, that the sample size of hunter-gatherers is small and there might be something unusual about the Unangans.
He said they lived in semi-underground homes that contained fires for cooking and heat and also oil lamps for light. Thus, he said, smoke inhalation may have overwhelmed the lack of traditional risk factors for atherosclerosis in the population.
Legacy of the Horus Study
Thomas expressed "how remarkably fun it is from a scientific standpoint" to search for atherosclerosis in ancient populations, comparing it to performing a virtual autopsy on someone from 4,000 years ago.
The overall message of the study so far is "that we as researchers in atherosclerosis need to look harder and further for other unknown risk factors," Thomas said. "We tend to be too smug that we understand why people get atherosclerosis, but I'm confident that we're missing something."
Even today, cardiologists "not infrequently" see patients with coronary disease that has no clear explanation, Thomas said.
"I hope that's our legacy: that we need to look further as to what causes atherosclerosis," he said.
Another way he hopes their research can help patients is by easing some of the blame felt by patients when they're diagnosed.
Thomas recounted a story of one of his patients who had developed atherosclerosis around age 40. After the first Horus study expedition and publication of the results, Thomas asked him how the research on mummies had affected him. The patient said that he quit blaming himself for getting the disease.
"So when I see a patient now with atherosclerosis who's had a heart attack, for example, I explain that they shouldn't be blaming themselves, that it's part of our genes and part of the human environment that we live in," Thomas said.
But that's not to say that all responsibility for managing the risks for atherosclerosis should be removed from individuals, he added.
"I think what the research shows is that we're all at risk for atherosclerosis," Thomas said. "That whether we live now or we lived 4,000 years ago we're at risk for atherosclerosis. So we should do the things we know delay it and avoid traditional risk factors, but we should also as scientists continue to look for risk factors that have been undiscovered to date."