How Black Death Kept Its Genes But Lost Its Killing Power

By Katherine Harmon
(Click here for the original article)

In five years, Black Death wiped out an estimated 30 to 50 percent of Europe's population. This medieval plague was caused by the bacteriumYersinia pestis, whichstill circulates among humans. Genetic clues as to what might have made it so deadly, however, had remained interred with the tens of millions of victims.

After careful extraction of genetic material from victims' teeth, a team of researchers has sequenced 99 percent ofthe Plague's genome—the first whole-genome reconstruction of a disease from skeletal remains.The draft genomeis described online October 12 inNature. (Scientific Americanis part of Nature Publishing Group.)

The 660-year-old plague DNA was isolated from four victims, who had been exhumed from London's East Smithfield Cemetery in the 1980s by the Museum of London Archaeology. To get samples from the skeletal remains, physical anthropologist Kristen Bos of McMaster University in Ontario and a colleague found themselves "wiggling the teeth out of the skulls at the Museum of London," she said in a Tuesday press briefing about the new study.

After carefully extracting genetic material from the inner pulp chamber of the teeth (so as not to damage their exteriors), the team created what Bos called a genetic "fishing rod," baited with molecules frommodern-dayY. pestis. With that as a lure, "we were able to essentially fish out the small preserved fragments ofYersinia pestisDNA" and separate it from the stew of human, bacterial and other genetic material that had accumulated during centuries in the soil. (The team described the actual method, which uses high-throughput DNA sequencing and microRNA enrichment, inan AugustProceedings of the National Academy of Sciencespaper.)

The genome now gives researchersa sort of "fossil"to start to map out the bacterium's phylogenetic tree. They discovered that the Black Death that devastated Europe between 1347 and 1350 was likely close to the common ancestor of all extantY. pestisstrains, (which likely arose—from the soil bacteriumYersinia pseudotuberculosis—between 1200 and 1340).

If this was "the first big pandemic with disseminatedYersinia pestisin humans," as Johannes Krause, of the University of Tᅢᄐbingen's Institute for Archaeological Sciences, asserted at the briefing, then previous plagues, such as the sixth-century Plague of Justinian, were either caused by a completely different pathogen or by a strain ofY. pestisthat proceeded to go completely extinct.

The new family tree can also help researchers examine related groups, such as the types of plagues that currently affect only rodents (such asMicrotusstrains and those that have been found in Chinese marmots)—and what genetic changes might need to occur to allow them to infect humans.

The sequenced strain has some 4.7 million base pairs. When compared with the modern version (based on 17 different genomes), there are just 90 genetic substitutions. That such few genetic changes occurred over the years, Krause said, was "really surprising."

Among these changes, none obviously explains ancient Black Death's virulence, Hendrik Poinar, also of McMaster, said during Tuesday's prepublication briefing. "There's no particular smoking gun."

So if the slight genetic differences in the disease were not responsible for its drastic change, what did make it so deadly in the 14th century that, as Bos described it, "people honestly thought it was the end of the world"?

Much of the mortality might be explained by situational factors, Poinar explained. Cooler climatic conditions and an excess of rain had led to failed crop harvests and widespread hunger, in addition to large numbers of people living in crowded—andalready pathogen-filled—medieval cities. "You probably had an immunocompromised population, living under very stressful conditions," Pointer said. Add to that a "population being hit byY. pestismaybe for the first time," and "Black Death was the perfect storm."

Humans have also adapted to the disease. The global population has likely built up some immunity from centuries of exposure to the pathogen. And even before the modern era, virulence was likely quelled by cultural adaptations, Krause noted. During the first outbreak, no one knew what kind of disease it was nor how to treat it, he said. During subsequent outbreaks, however, "people had already developed some kinds of adaptations—they had developed quarantines, they had developed first aid to treat patients with the symptoms."

And in the meantime, we have developed evenmore sophisticated surveillanceand treatment options, Poinar pointed out. So even if a strain ofY. pestiswere to acquire a new batch of mutations, it would still likely be no match for contemporary antibiotics. But that doesn't mean we're in the clear, he added. With increased global interaction andmore climatic changeson the way, "that will, of course, lead to other zoonotic events where viruses or bacteria can transfer from animals or hosts into the human population," Poinar said.

For more on old-time diseases, click through this slideshow from The Huffington Post:

Bubonic Plague

Yes, the black plague -- responsible for <a href="http://www.smithsonianmag.com/people-places/mall_aug99.html?c=y&page=2" target="_hplink">killing 56 million people in Europe the 14th century</a> -- is still around, but it isn't as deadly or prevalent as it was in Medieval times. Dr. Robert Gaynes, an infectious disease expert at Emory University and author of the book <a href="http://estore.asm.org/viewItemDetails.asp?ItemID=1036" target="_hplink">Germ Theory: Medical Pioneers in Infectious Diseases</a>, said that people contract the disease when they gain access to previously undistrubed ecosystems, thereby making "these types of diseases become evident as a result of animal contact."   These days, the disease is most commonly spread by bites from fleas that are infected with Yersinia pestis. When the bacteria enters into a person's skin, it leads to headache, chills, and <a href="http://www.bt.cdc.gov/agent/plague/factsheet.asp" target="_hplink">swollen lymph glands</a>, according to the CDC. Early <a href="http://www.bt.cdc.gov/agent/plague/factsheet.asp" target="_hplink">treatment with antibiotics</a> is essential for survival, as the disease can cause respiratory failure and shock if left untreated.   Every year, about 1,000 to 3,000 <a href="http://healthland.time.com/2011/05/10/first-case-of-bubonic-plague-in-2011-appears-in-new-mexico/" target="_hplink">bubonic plague cases</a> occur around the world, with 10 to 20 of those cases in the United States, <em>TIME</em> reported. The first 2011 case of bubonic plague was confirmed in May in a New Mexico man.   The reason is murky for why black plague seems to be less deadly today than in the Medieval times, Weinberg said, but it probably has to do with more rats and unclean living conditions back then, as well as a lack of appropriate medicines. In addition, the bacteria back then may be different from the current form, he added.

Scarlet Fever

<a href="http://www.medicinenet.com/scarlet_fever/article.htm#history" target="_hplink">Scarlet fever</a> was among the rash of diseases that commonly afflicted people in the 19th century (alongside yellow fever, rubella and measles), according to MedicineNet. Scarlet fever most often afflicts children, causing rash and fever.  Fortunately, scarlet fever is a lot less common today than it was centuries ago, but it still can be deadly. Today, we now know that scarlet fever is just a form of group A streptococcus (strep), Weinberg said. But instead of just turning into a regular case of strep throat, scarlet fever manifests as a red skin rash.   With antibiotics, the disease is easily treated, though complications can occur that <a href="http://www.medicinenet.com/scarlet_fever/article.htm#history" target="_hplink">can lead to sepsis</a> (bacteria in the blood, tissue or bone), according to MedicineNet. Just this summer, Reuters reported that a Hong Kong kindergarten was closed after tests revealed that a child there may have <a href="http://www.reuters.com/article/2011/06/21/us-scarletfever-china-idUSTRE75K14Q20110621" target="_hplink">died from scarlet fever</a>. Scarlet fever is relatively common in that part of the world, but this year a Hong Kong health department spokesman told Reuters that there seem to be more cases of it this year than in past years.

Whooping Cough

<a href="http://articles.sfgate.com/2011-09-20/bay-area/30178479_1_whooping-cough-booster-shots-childhood-vaccine" target="_hplink">Whooping cough</a>, caused by the Bordetella pertussis bacteria, was a common illness among children in the early 1900s, according to HealthCentral. However, when the vaccine for whooping cough was introduced in the 1940s, cases dropped. But while whooping cough cases are still dramatically lower than 50 years ago, there are still cases that persist today possibly because the vaccine against the disease doesn't provide lasting protection later in life, Weinberg said.   Another reason is that older people seem to be able to carry whooping cough in their throats without actually getting sick (due to being vaccinated at a younger age),  but that whooping cough is then passed on to infants who haven't yet been vaccinated against the disease, Gaynes said.   "This problem has led to a recent recommendation by [the] CDC to have adults get TDAP once as adults (it contains pertussis in the vaccine) and not just a tetanus booster, which is needed every ten years," Gaynes told HuffPost.   Recent research presented just last month shows that the <a href="http://articles.sfgate.com/2011-09-20/bay-area/30178479_1_whooping-cough-booster-shots-childhood-vaccine" target="_hplink">protection from the whooping cough vaccine</a> is decreased dramatically once a child reaches age 8 or 9, the <em>San Francisco Chronicle</em> reported.   <a href="http://www.cdc.gov/features/pertussis/" target="_hplink">Whooping cough is very contagious</a> -- spread by cough and sneezing -- and is so named because of the sound people who have it make when they cough. Last year, 27,550 people had whooping cough in the United States, according to the CDC. The disease is the deadliest for babies, as it can lead to pneumonia, convulsions and even death.

Polio

Polio, the paralysis-causing disease that afflicted former president Franklin D. Roosevelt, isn't completely gone from the world today. However, it has been eliminated from the western world, Weinberg said. The Mayo Clinic reports that the last known <a href="http://www.mayoclinic.com/health/polio/DS00572" target="_hplink">case of polio in the U.S.</a> was in 1979.   Polio is still present in <a href="http://www.who.int/mediacentre/factsheets/fs114/en/" target="_hplink">Afghanistan, Pakistan, India and Nigeria</a>, where unrest and dangerous conditions can make it more difficult to get everyone vaccinated against the disease, according to the World Health Organization. Recently, the WHO reported that a dangerous strain of polio -- called wild poliovirus type 1 -- had <a href="http://www.huffingtonpost.com/2011/09/20/polio-china-pakistan_n_971787.html" target="_hplink">made its way from Pakistan to China</a>.   Polio<a href="http://www.mayoclinic.com/health/polio/DS00572" target="_hplink"> causes paralysis</a> and can make it hard to breathe, the Mayo Clinic reported. It can even lead to death.

Gout

Gout has been known throughout history as the "<a href="http://www.bl.uk/learning/langlit/booksforcooks/1700s/1700sfood.html" target="_hplink">disease of kings</a>" and the "rich man's disease," as it was most commonly seem among the gluttonous rich in the 1700 and 1800s, according to the British Library. Gout is considered an ancient form of <a href="http://www.cdc.gov/arthritis/basics/gout.htm" target="_hplink">inflammatory arthritis</a>, and is caused by metabolic disorder that has not been properly controlled. It occurs when uric acid crystals build up in tissues and fluids, thereby leading to a red, swollen joint that is very painful, according to the Centers for Disease Control and Prevention. The condition is most common in overweight men and women who have gone through menopause.  Gout rates have <a href="http://arthritis.webmd.com/news/20101110/gout-cases-on-the-rise-in-u-s" target="_hplink">been on the rise</a> since the 1960s, with cases doubling between 1960 and 1990 and then continuing to rise through 2008, according to WebMD. More than 8 million Americans currently have gout.   WebMD reported that the <a href="http://arthritis.webmd.com/news/20101110/gout-cases-on-the-rise-in-u-s" target="_hplink">rise in gout cases</a> may be due to people living longer, as the condition is seen in women only after they have passed menopause. In addition, "you can go years with hyperuricemia and no symptoms. But at some point, enough uric acid accumulates to have a flare-up of gout, so if you're living longer you are more likely to reach that threshold," gout expert Dr. John S. Sundy told WebMD.   In addition, Gaynes speculated that it may not even be that gout rates are actually rising -- rather, detection and diagnosis may have improved throughout the years.

This article originally appeared on HuffPost.