Plague Immunity Gene Stops HIV Aids

       A Gene Found to Protect Against the Plague Stops Aids.

In September 1665, George Viccars, a tailor in the small, central-England village of Eyam, received a parcel of cloth ridden with plague-infected 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?

             Turns out this gene stops Aids dead in its tracks.

                             Plague Gene Stops Aids

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.

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. 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, central-England village of Eyam, received a parcel of cloth ridden with plague-infected 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 plague-ravaged 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.

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, 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 principle 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 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

Comments

[Phoenix]

I love this. Good report. I became interested in genetics and read three of Matt Ridley's books: GENOME; THE RED QUEEN ; and NATURE vs. NURTURE. He predicts that the whole of medicine will turn on the discoveries made by mapping the human genome. It is too fascinating.

Anyway, if you're interested, Google Matt Ridley and see about him. The red queen analogy is from Alice in Wonderland - where the red queen is always running but getting nowhere as the landscape continues to pass her by. That analogy is part of his theory of how the study of genetics and all its possibilities is going far too fast for us to keep up with our applications. Very neat reading.

[Mouse]

It is very fascinating and I really do hope they can figure out the gene - disease connection soon! There is so much that could do with correcting in the way of illness. I have always believed that there is a link between our genes and their interaction with the stuff we put in our faces and around our bodies. You know, like when you get new shower curtains, and they smell so vinyl, for days! That means that their little molecules are bombarding the air you live and breathe in. Toxic mold is probably better for you!

[Phoenix]

Nice thought, Mouse. Yuk. But I already knew that. Years ago someone asked Marilyn Vos Savant if smell had essence. She said, of course. I have no idea what I thought before reading that....that smell was some innocuous vapor or something. But from that time on, I've thought about 'smell' and its essence and how breathing in that essence has to do something. Since then, I always run when someone farts. The very thought I might have about a zillion fart molecules on me just trashes me. I think I'll go to Ask Jeeves and see if I can find out if a fart molecule has bacteria on it. OH YUK! Maybe I won't. Oh...think of your new car smell that lasts for months and months!

Nature vs. Nurture talks all about our genes and what we do to ourselves and how this leads to disease or not.

[Steel]

Ummm ...

Those would be farticles. The smallest, indivisible iota of shit.

[Obi-Wan]

I think I'll go to Ask Jeeves and see if I can find out if a fart molecule has bacteria on it. OH YUK! Maybe I won't.

Hehheh...you are SO funny sometimes, Phoenix!

But don't worry--a single "farticle" molecule is way too small to have any bacteria riding around on it. A glucose molecule, for example, is about 1/1000th the diameter of the average bacterium (0.9nm vs. about 1000nm).

[Phoenix]

You boys think you're so smart. Me? I'm not taking any chances. Anyone farts and I'm outta there. Of course, *I* do not fart, BUT.. if I did, I would run.

[Mouse]

Oh, oh! I married into a family of farters! And I have been making sure my loved ones eat plenty of it too. When I look at food labels, I check the sodium level first, if that's okay I go on to the fiber count. The bigger the better. Vinyl molecules put more fear in me. And those things they call clean air fragrances are scarier (is that a word?) than vinyl!

[Phoenix]

A family of farters.... HA HA HA. So, Mouse, they mess up your gene pool ? Of course, I KNOW you would never fart. It must be love. Lawww, what a girl puts up with for love.

I have to agree with you about those fresh-air sprays! I bought one once and used it and the 'air' just about shut my lungs down. I was gasping and fumbling for my albuterol. Scary.

We had a couple of labs years ago, and one day my old-lady neighbor came by to chat. We were on the back deck talking away when one of the labs came up and starting rolling around and stretching. She started farting - these loud reverberating farts one after another. I was like....ohmygod....I am going to bust a gut here any second. After one particularly loud expulsion, my sweet neighbor couldn't help but jerk her head over to the dog, but she kept on talking like nothing was going on. I swear I almost wet my pants I wanted to laugh soooo bad. Dumb dog just kept it up until the neighbor finally left. It would have been so much easier if my neighbor had muttered, "Nice rip, Franny.", but, of course, she was too much a lady - unlike me who wanted to throw my head back and howl at the heavens. hahahaha...

[Mouse]

Canines do do it better! They have absolutely no inhibitions. Lucky dogs! Some of those air fresheners cause my lungs to go liquid too. I run when I get a whiff of those things. My direct line gene pool is more in the line of slobbering, drooling, and spitting while you speak stuff. We don't fart either! Oh no, wait a minute. I do have a cousin who farts while he is walking. He moves along as if nothing is happening. He is somewhat elderly, so maybe he doesn't hear it and figures that no one else can. Does a fart make a noise when there's no one around to hear it? Ho Ho Ho!

[Phoenix]

ooooooooooooooooh................ hee hee... hahahahaha... Do tell, Mouse. You must be of German lineage what with all the spitting when you talk.. HAHAHA !! So, Cousin Fahtah walks and farts at the same time? DAMN! That's some talent. I mean, it sure beats chewing gum and walking. 'Course Cousin Fatah, bein' from your side, can spit, walk and faht at the same time.

One time we took the kids to Disneyworld. Long trip that entailed a gang-rush into the gas station stores to get goodies with each fill-up of our Suburban. Parker got a large pack of sugarless gum. I don't know that he meant to get sugarless, but he did and out of boredom we all chewed some. Then we all chewed some more and finally emptied the whole thing. We were riding along in silence when the first odiferous cloud infiltrated the truck to absolute shouts of 'oh gross!' 'Damn!' 'PEEEW!!' That was it. All of is found out we were allergic to aspartame, and all of us just hammered the atmosphere for a good two-hundred miles. Silent but deadly these things were. oh.... We had the windows open and the kids were griping about being blown to death......... hahahaha.....

Do you have to hear a fart to smell it??? NOOOOOOOO!!

[Fré]

Only a 15% of the people survived not half the town
In fact delta 32 is only found by 14% of the people not 50%