The Darwin Awards Countdown to Extinction (24 page)

 

 

1999 | Our 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!
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
that I had won the Dumbass Award.

 

Reference: Anonymous

 

 

How do we get cancer? In one word,
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 arsenal 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.

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.

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
supply. It does so by exuding chemicals that provoke an inflammation. To the immune system, this chemical Molotov cocktail signals mischief. It sends sentries called natural killer cells to the scene to attack the troublemakers with antitumor 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.

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 arsenal as needed. To amplify the attack, these elite commandos multiply at the tumor site, spawning 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:

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 assemble, transport, or display
any
antigens. Such cancer cells display no antigens at all, neatly flying under the immune radar in stealth mode

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
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 antitumor 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.

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!”
As a backup, cancer cells manufacture special proteins that break key stages in the self-destruction process.
“You can’t make me!”
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
(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.

To the traditional cancer treatments—radiation, surgery, chemotherapy—add another:
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!