1999Our hero had just moved into a rental home. The yard had not been mowed in more than a year, so he set about mowing down the overgrown weeds and soon ran right over a foot-wide hole. Out came flying a squadron of angry yellowjackets! As he ran in terror, our man knew he had to get rid of these vile pests somehow, and soon.
He sat on the porch pondering the problem over a few brews. As an interim solution, he poured a five-gallon jug of gasoline down the hole, then drank more beer and watched the sun set. What was the likelihood that the mission was accomplished? An hour later he decided to err on the side of caution and burn them out.
He lit a match and tossed it at the hole.
Boom, and I mean KABOOM! KABOOM! Hair on arms? Gone! Eyebrows? Gone! Walkway? Cracked, and a six-foot crater where the wasp nest had been. As he stood there, burned and smoking, beer in hand, wife shrieking in the background, he knew . . . Hair on arms? Gone! Eyebrows? Gone! Walkway? Cracked, and a six-foot crater where the wasp nest had been. As he stood there, burned and smoking, beer in hand, wife shrieking in the background, he knew . . .
Confession, I knew I knew that I had won the Dumba.s.s Award. that I had won the Dumba.s.s Award.
Reference: Anonymous
SCIENCE INTERLUDE EVOLVING CANCER.
By Chandra Shekhar
How do we get cancer? In one word, evolution evolution.
Toxins, viruses, radiation, errors in DNA copying, and other nasty triggers cause cancerous cells to form in our bodies. Fortunately our immune system kills them off, nipping nascent tumors in the bud. Now and then, however, a few bad cells survive. Multiplying furiously and mutating nonstop, they develop and deploy a vast a.r.s.enal of weapons to stay one step ahead of the immune system.
They hide. They sabotage. They subvert. They evade. They attack.
For awhile, the immune system fends them off using its own formidable weaponry. A precarious equilibrium sets in-as fast as the immune system kills the tumor cells, more resistant cells emerge with just the right genetic mix to survive the immune onslaught. At some point, the immune system loses the arms race. Unchecked, the victorious cancer cells run riot, growing in number, invading nearby tissue and spreading to new parts of the body.
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The result is a full-blown cancer made of cells that have eluded the immune system time and time again. By allowing only the wiliest tumor cells to survive and grow, the immune system-genetically speaking-sculpts the tumor. Such a tumor, in the words of Yale immunologist Richard Flavell, is essentially a Darwinian product. the tumor. Such a tumor, in the words of Yale immunologist Richard Flavell, is essentially a Darwinian product.
To defeat cancer, scientists must understand how the immune system tries-and fails-to do so.
Imagine defending a strategic installation-vast, vital, vulnerable-under constant attack by a relentless enemy that grows stronger with every setback. That is precisely the challenge the immune system faces in defending the body from cancer. To have even a hope of success, it must be vigilant, strong, swift, and versatile.
The immune system"s first job is to detect the threat. Like a squatter stealing electricity and building materials, a growing tumor remodels the tissue around itself and creates its own blood Cells display bits of protein called antigens antigens on their surface. Normal cells display normal antigens that the immune system learns to ignore. on their surface. Normal cells display normal antigens that the immune system learns to ignore.
supply. It does so by exuding chemicals that provoke an inflammation. To the immune system, this chemical Molotov c.o.c.ktail signals mischief. It sends sentries called natural killer cells to the scene to attack the troublemakers with ant.i.tumor compounds. The battle is on.
Another type of soldier now enters the fray. The dendritic (den DRIT ik) cell acts as a spy for the immune system. Damaged cells are normally good citizens; they mark themselves for destruction by displaying bits of defective proteins ("antigens") on their surfaces. Dendritic cells gather these antigens from dead tumor cells and go off to alert the rest of the body"s defenses.
The alerted immune system then trains a troop of elite commandos-T-cells-for a single mission: Kill all cells sporting these specific tumor antigens. When these new troops arrive at the tumor site, armed and ready, the battle is in full swing.
The immune system is vigilant, strong, and versatile.
Killer T-cells attack tumors using a pair of toxins: one to pierce cells, and the other to kill from within. Besides this one-two punch, T-cells have another strategy: special compounds that send "death signals" to tumor cells, forcing them to commit suicide. Using these weapons, T-cells kill many enemies, replenishing their toxic a.r.s.enal as needed. To amplify the attack, these elite commandos multiply at the tumor site, sp.a.w.ning fresh troops. And using trophy antigens taken from their victims, they train the immune system to better attack future cancers of the same type.
Cancer cells don"t stand a chance, seemingly.
The reality is quite different. The immune system is indeed vigilant, strong, swift, and versatile. But in cancer, it meets its match. For every immune thrust, cancer has an effective parry, and an equally lethal counterthrust-often turning the immune system"s own weapons against it. Here is what it does: [image]
Hide. The immune system expects defective cells to identify themselves using antigens. Not surprisingly, this mechanism is broken in most cancer cells. In some cases, they disguise themselves by displaying only normal cell antigens. In other cases, convenient genetic mutations knock out proteins needed to a.s.semble, transport, or display any any antigens. Such cancer cells display no antigens at all, neatly flying under the immune radar in stealth mode antigens. Such cancer cells display no antigens at all, neatly flying under the immune radar in stealth mode [image]
Sabotage. Cancers secrete a substance that stops dendritic cells from gathering their antigens, thus hamstringing an effective immune response. They emit a range of other immune-suppressing agents such as vascular endothelial growth factor (VEGF), which not only suppresses the body"s defenses, but also helps create a pirate blood supply to feed the growing army of invader cells.
Subvert. Cancers create their own microenvironment that serves as a fortress against attack by the immune system. Using chemical signals, they attract immature immature immune cells from their birthplace in the bone marrow. These callow recruits have not been trained in the immune system"s boot camp, and lack ant.i.tumor capability-yet their presence repels mature immune cells. Tumors also take hostage a number of regulatory T-cells, suppressing the immune response. Designed to protect normal cells from the immune system, these pacifist regulatory T-cells end up protecting the tumor instead. immune cells from their birthplace in the bone marrow. These callow recruits have not been trained in the immune system"s boot camp, and lack ant.i.tumor capability-yet their presence repels mature immune cells. Tumors also take hostage a number of regulatory T-cells, suppressing the immune response. Designed to protect normal cells from the immune system, these pacifist regulatory T-cells end up protecting the tumor instead.
Cancer has an effective parry for every immune thrust.
Evade. When asked, well-behaved body cells go peacefully to their graves by triggering an internal self-destruct mechanism. Cancer cells act differently. They often avoid self-destruction by losing cell surface molecules designed to receive death signals from T-cells. Picture a willful child, fingers in ears, saying, "I don"t hear you!" "I don"t hear you!" As a backup, cancer cells manufacture special proteins that break key stages in the self-destruction process. As a backup, cancer cells manufacture special proteins that break key stages in the self-destruction process. "You can"t make me!" "You can"t make me!" They also neutralize T-cell toxins with a compound that immune cells themselves use for self-protection. They also neutralize T-cell toxins with a compound that immune cells themselves use for self-protection.
Attack. Tumors release free radicals, reactive chemicals that weaken or kill immune cells. They secrete compounds that induce natural killer cells to commit suicide or even fratricide. They turn the T-cell"s death signal against it, and the T-cell obediently commits suicide-as it tried, and failed, to force the cancer cell to do!
As Professor Flavell puts it, "Cancer has a long, long shopping list of tricks."
Fortunately for us, these tricks are not infallible. Don"t tell the tumors, but life may soon get much tougher for them.
Selective evolution notwithstanding, sick cells cannot help but look different from healthy cells. A close scrutiny usually reveals distinctive compounds, or markers, on their surfaces. Once we know the markers for a type of cancer, we can design drugs that precisely attack it. One such drug, trastuzumab trastuzumab (Herceptin (Herceptin ), already treats a common type of breast cancer.
Even better, researchers are exploring ways to train the immune system to recognize bad cells by vaccinating with cancer antigens, promoting a stronger, quicker attack. Further, they are designing drugs that help the immune system fight cancer"s dirty tricks. These drugs destroy immune-suppressing tumor compounds, recruit immune cells to the tumor, revive weakened immune cells, or force tumor cells to heed death signals.
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To the traditional cancer treatments-radiation, surgery, chemotherapy-add another: immunother apy immunother apy. It is poised to hit the clinic in the near future. The survival skills of cancer are going to be tested like never before. Can they evolve fast enough to cope with evolving medicine? Stay tuned, and keep your fingers crossed!
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REFERENCES:.
D. Gabrilovich and V. Pisarev, "Tumor escape from immune response: Mechanisms and targets of activity," Current Drug Targets Current Drug Targets 4(7) (2003), 525-536. 4(7) (2003), 525-536.
R. Kim, M. Emi, K. Tanabe, "Cancer immunoediting from immune surveillance to immune escape," Immunology Immunology 121(1) (2007), 1-14. 121(1) (2007), 1-14.
CHAPTER 4.
ELECTRICITY: COMMON GROUNDS.
"I know we shouldn"t make fun of the misfortunes of others, but I couldn"t help myself!"
-Fan mail
Electricity is often the shortest path to a "vivid" demise. Spectacular failures result from the combination of wires, water, and human circuit breakers in a series of spectacular and galvanizing stories. Read onward for amusing and illuminating electrical emergencies.
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One Foot in the Pool * An Illuminating Story * Tiny Elec Fence * Electric Bathtub Blues * Tennessee Pee * Shocking Rappel * Shockingly Conductive * Christmas Light Zinger [image]
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Darwin Award Winner: One Foot in the Pool Confirmed by Darwin Featuring electricity and water!
24 AUGUST 2008, JAKARTA, INDONESIACharles had just completed his International Baccalaureate at King William"s College in the Isle of Man. The princ.i.p.al of the college posthumously described him as "a very bright boy with a very bright future." He planned to retire by the age of thirty.
Unfortunately for Charles, his elite education omitted an important lesson from the curriculum: the danger of electricity.
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He had one foot in the backyard swimming pool when he noticed a cement box full of electrical wires near the edge of the pool. It was a junction box supplying power to the Jacuzzi. Curious, Charles started to fiddle with a fistful of colored wires and was immediately rooted to the spot by 240 volts of electrical energy surging through his body.
A bright future and early retirement were, indeed, in his cards.
Reference: iomtoday.co.im [image]
Reader Comment
"Charles was a real live wire!"
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Darwin Award Winner: An Illuminating Story Confirmed by Darwin Featuring electricity, weather, and a frugal old fart
26 FEBRUARY 2008, FRANCEA seventy-one-year-old pensioner reached a shocking conclusion when his frugal attempt to illuminate his yard with power siphoned from the National Grid backfired spectacularly.
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The gentleman in question illegally opened a major power junction box at the front of his house, intending to hard-wire a cable to his garden shed. Unfortunately he attempted to do this rewiring during a major downpour. The result was all too predictable. The poor chap was immediately rooted to the spot, and declared DART (Darwin Award Right There) at the scene.
Lessons: 1. 1. Don"t Don"t wire your shed to a local power substation. wire your shed to a local power substation.2. Don"t Don"t wire your shed in the rain wire your shed in the rain. 3. And there is such a thing as being too frugal. 3. And there is such a thing as being too frugal.
Reference: Ouest-France, rennes.maville.com [image]
Darwin Award Winner: Zap Car10 Confirmed by Darwin Featuring electricity and vehicles
10 JANUARY 2010, BRAZILAn electrical discharge made toast of munic.i.p.al guard Arthur C., forty-seven. According to police reports, he had installed a tiny electric fence around his car to protect against the frequent robberies that occur in his neighborhood in Belem in the state of Para. Better safe than sorry. Then one evening he forgot that he had left the current on. Let"s just say his forgetfulness caused him quite a shock. Galvanic shock.
We are all dying, but some are more eager than others.
Reference: oglobo.globo.com Historic Darwin Award Winner: Electric Bathtub Blues Confirmed by Darwin Featuring electricity, water, and a lightbulb [image]
11 MARCH 1978, FRANCEThe singer Claude Francois, whose stellar career can be compared to that of legendary Elvis Presley, popularized rock"n"roll in France. One evening, he returned to his Paris apartment from a busy touring schedule and ran a quiet bath. While standing in the steaming water in the tub, he noticed some wires dangling from the ceiling light. These wires had been the subject of numerous complaints in his various correspondences! The naked singer reached out and grabbed hold of the naked wires . . . and was electrocuted then and there.
Au revoir, Claude.
Reference: Wikipedia and online French TV archives Researched by the indomitable Ariane La Gauche [image]
Reader Comment
"How do you p.r.o.nounce that, Claude or Clod?"
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Darwin Award Winner: Tennessee Pee Unconfirmed Featuring electricity, alcohol, gravity, and bees