Download Article, Black Plague_Inherited Immunity

Inherited Immunity- by Viki Babcock (LESSON PLAN w punnets)
Case File: Mystery of the Black Death
Background (LINK TO ARTICLE BELOW)
No one knows exactly why, but in the late 1320s or early 1330s, bubonic plague broke out in
China's Gobi desert. Spread by flea-infested rats, it didn't take long for the disease to reach
Europe. In October of 1347, a Genoese ship and crew returning from the Black Sea -- a key
trade link with China -- landed in Messina, Sicily. Most of those on board were already dead,
and the ships were ordered out of harbor. But it was too late. The town was soon overcome
with pestilence, and from there, the disease quickly spread north along trade routes -through Italy and across the European continent. By the following spring, it had reached as
far north as England, and within five years, it had killed 25 million people -- one-third of the
European population.
 No one knows exactly why, but in the late 1320s or early 1330s, bubonic
plague broke out in China's Gobi desert.
 Spread by flea-infested rats, it didn't take long for the disease to reach
Europe.
 In October of 1347, a Genoese ship fleet returning from the Black Sea -- a key
trade link with China -- landed in Messina, Sicily.
 Most of those on board were already dead, and the ships were ordered out
of harbor. But it was too late.
 The town was soon overcome with pestilence, and from there, the disease
quickly spread north along trade routes -- through Italy and across the
European continent.
 By the following spring, it had reached as far north as England, and within
five years, it had killed 25 million people -- one-third of the European
population.
1. What question(s) came to you as you were reading?
Write them down.
a) ________________________________________________?
b) ________________________________________________?
c) ________________________________________________?
2. Make an inference related to dates, time periods, or statistics in
the paragraph above.
3. Make an inference (infer) the meaning of one unfamiliar word by
using the clue words around this word contained in the text
(context clues).
The bubonic plague is caused by a bacterium called Yersinia pestis and
is characterized by chills, fever, vomiting, diarrhea, and the formation
of black boils in the armpits, neck, and groin. Though the disease was
originally called the "Great Mortality" and the "Great Pestilence," the
name "Black Death" was eventually adopted because of these black
boils, which derive their color from dried blood under the skin caused
by internal bleeding. In certain cases the bacterium spreads to the
victims' lungs, causing them to fill with frothy, bloody liquid. This
derivation of the disease is called pneumonic plague, and can quickly
spread from person to person through the air. It is almost always
lethal.
The plague first spread to Britain in 1348, travelling from Bristol to
Oxford and London in several days. More than three hundred years
later, in 1665, perhaps the worst of the English epidemics broke out in
London. That summer, the nobility and clergy fled the city, as some
7,000 people died each week. As many as 100,000 lives were lost
before winter killed the fleas and the epidemic tapered off.
Contemporary medicine could provide no explanation for the sickness,
and most doctors were afraid to offer treatment. In an attempt to keep
from being infected, the few physicians who did risk exposure wore
leather masks with glass eyes and a long beak filled with herbs and
spices that were thought to ward off the illness. Even one person in a
household showing plague-like symptoms was enough to mandate a
40-day quarantine for the whole home -- a virtual death sentence for
everyone living in it.
In September 1665, George Viccars, a tailor in the small, centralEngland village of Eyam, received a parcel of cloth ridden with plagueinfected fleas from London. Four days later, Viccars died. By the end of
the month, five more villagers had succumbed to the plague. The
panicked town turned to their rector, William Mompesson, who
persuaded them to quarantine the entire village to prevent the
bacterium from spreading throughout the region. It seemed like
suicide. A year later, the first outsiders ventured into Eyam, expecting
a ghost town. Yet, miraculously, half the town had survived. How did
so many villagers live through the most devastating disease known to
man?
Local Eyam lore tells befuddling stories of plague survivors who had
close contact with the bacterium but never caught the disease.
Elizabeth Hancock buried six children and her husband in a week, but
never became ill. The village gravedigger handled hundreds of plagueravaged corpses, but survived as well. Could these people have
somehow been immune to the Black Death?
Dr. Stephen O'Brien of the National Institutes of Health in Washington
D.C. suggests they were. His work with HIV and the mutated form of
the gene CCR5, called "delta 32," led him to Eyam. In 1996, research
showed that delta 32 prevents HIV from entering human cells and
infecting the body. O'Brien thought this principle could be applied to
the plague bacteria, which affects the body in a similar manner. To
determine whether the Eyam plague survivors may have carried delta
32, O'Brien tested the DNA of their modern-day descendents. What he
found out was startling. ...
Clues and Evidence
For a disease-causing microorganism to infect the human body there must be a gateway or portal through which it
enters into human cells. The plague bacterium works this way, hijacking the white blood cells sent to eliminate it.
Traveling inside the white blood cells to the lymph nodes, the bacteria break out and attack the focal point of the
human immune system. Dr. Stephen O'Brien felt that the mutated CCR5 gene, delta 32, may have prevented the
plague from being able to enter its host's white blood cells.
Eyam provided O'Brien an ideal opportunity to test this theory. Specifically, Eyam was an isolated population known
to have survived a plague epidemic. Everyone in the town would have been exposed to the bacterium, so it's likely
that any life-saving genetic trait would have been possessed by each of these survivors. "Like a Xerox machine,"
says O'Brien, "their gene frequencies have been replicated for several generations without a lot of infusion from
outside," thus providing a viable pool of survivor-descendents who would have inherited such a trait.
Knowing who died and who lived through the early years of the plague is somewhat problematic. Deaths among the
general English population were not recorded in the 14th Century -- the height of the Plague -- and most
communities did not begin recording parish registers until around 1538. Fortunately, Eyam began keeping a parish
register in 1630. Thus historian John Clifford began by examining the register, noting everyone who was alive in
1665, the year the plague came to Eyam. He searched for evidence of life through the year 1725 -- marriages,
baptisms, burials that took place years after the plague had left the village. Deleting the names of those lost during
the plague period, he was able to determine who the survivors were.
DNA samples could only be collected from direct descendents of the plague survivors. DNA is the principal
component of chromosomes, which carry the genes that transmit hereditary characteristics. We inherit our DNA from
our parents, thus Eyam resident Joan Plant, for instance, may have inherited the delta 32 mutation from one of her
ancient relatives. Plant can trace her mother's lineage back ten generations to the Blackwell siblings, Francis and
Margaret, who both lived through the plague to the turn of the 18th century. The next step was to harvest a DNA
sample from Joan and the other descendants. DNA is found in the nuclei of cells. The amount is constant in all
typical cells, regardless of the size or function of that cell. One of the easiest methods of obtaining a DNA tissue
sample is to take a cheek, or buccal, swab.
After three weeks of testing at University College in London, delta 32 had been found in 14% of the samples. This is
a genetically significant percentage, yet what, really, did it mean? Could the villagers have inherited delta 32 from
elsewhere, residents who had moved to the community in the 350 years since the plague? Was this really a higher
percentage than anywhere else? To find out, O'Brien assembled an international team of scientists to test for the
presence of delta 32 around the world. "Native Africans did not have delta 32 at all," O'Brien says, "and when we
looked at East Asians and Indians, they were also flat zero." In fact, the levels of delta 32 found in Eyam were only
matched in regions of Europe that had been affected by the plague and in America, which was, for the most part,
settled by European plague survivors and their descendents.
Meanwhile, recent work with another disease strikingly similar to the plague, AIDS, suggests O'Brien was on the
right track. HIV, the virus that causes AIDS, tricks the immune system in a similar manner as the plague bacterium,
targeting and taking over white blood cells. Virologist Dr. Bill Paxton at the Aaron Diamond AIDS Research Center in
New York City noticed, "the center had no study of people who were exposed to HIV but who had remained
negative." He began testing the blood of high-risk, HIV-negative individuals like Steve Crohn, exposing their blood to
three thousand times the amount of HIV normally needed to infect a cell. Steve's blood never became infected. "We
thought maybe we had infected the culture with bacteria or whatever," says Paxton. "So we went back to Steve. But
it was the same result. We went back again and again. Same result." Paxton began studying Crohn's DNA, and
concluded there was some sort of blocking mechanism preventing the virus from binding to his cells. Further
research showed that that mechanism was delta 32.
Scientists studying HIV first learned about the gateway-blocking capacity of the CCR5 mutation in 1996. Several
drug companies, then, quickly began exploring the possibility of developing pharmaceuticals that would mimic delta
32 by binding to CCR5 and blocking the attachment of HIV. Previous methods of treatment interfered with HIV's
ability to replicate after the virus has already entered a cell. This new class of HIV treatment, called early-inhibitor -or fusion-inhibitor -- drugs seek to prevent the virus from ever attaching at all. These pharmaceuticals are still in
relatively early stages of development, but certainly stand as a hopeful new method of approaching HIV treatment.
SECRETS OF THE DEAD is a production of Thirteen/WNET New York.
© 2004 Educational Broadcasting Corporation. All rights reserved.