Click here to Download An Elegant Defense PDF Book by Matt Richtel Language English having PDF Size 7.8 MB and No of Pages 372.
His silver minivan, fast approaching Denver from its suburbs, looked like scrap metal on wheels. The heater coughed and spat and seemed to work only when it was hot outside. The back door didn’t open. Various warning lights dotted the dashboard, alerting Jason to system failures he ignored. His maps and atlases overflowed compartments and littered the floor.
An Elegant Defense PDF Book by Matt Richtel
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Then there was the smell. It permeated the cabin from the five-gallon gasoline jerry can he kept in back for emergencies, and from the accumulated greasy residue from endless fast-food stops. Jason could never resist 7-Eleven rotisserie hot dogs, despite referring to them as “witches’ fingers” and “disgusting.”
When Jason went on cross-country sales trips, which was often, he would sometimes sleep in the back of the van. He’d curl up on a stained orange Oriental rug, his head next to the gas can. Or he’d slumber on top of the boxes of shiny, bejeweled trinkets that he sold to far-flung casinos for use as promotional items.
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Jason was forty-seven, with an undergraduate diploma from an elite college, graduate degrees in business and law, and no reliance on or particular reverence for those trappings. He lived from one entrepreneurial idea to another, one adventure to the next. Never was he happier than when he was driving, a dip of Skoal Fine Cut packed in his lip.
Rocking out to Springsteen or to a local station on the dial with some new town on the horizon. Jason was determined to discover, explore, and live his way. He was a genuine American dreamer and the van his covered wagon. “Ma, if anything ever happens to me, I want the van taken care of. Are you listening, Ma?” he told his mother.
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Jason and his mother, Catherine, alternately cherished each other and fought with vicious visceral passiveaggressive dialogue that would make Arthur Miller melt. Now Jason sat in the passenger seat, his girlfriend, Beth, driving. He was heading to pull off as unconventional a trick as even he could ever have conceived.
He was determined to become a medical marvel, a poster boy, as he termed it, for a miraculous new cancer treatment. Jason was going to defy death, while standing on its precipice, one foot already over the edge. Jason suffered from late, late-stage cancer. By any reasonable definition, it was terminal.
Fifteen pounds of Hodgkin’s lymphoma was lodged in his lungs and back on the left side of his body, and it was doubling in size every few weeks. Four years of chemotherapy and radiation had ultimately failed, managing to beat back for only brief periods what is typically one of the most curable of cancers. Doctors had tried nearly everything, some drugs twice or in combinations, with brutal side effects. An Elegant Defense PDF Book
The malignancy always returned. Now the tumor so protruded from his back that Beth affectionately referred to Jason as Quasimodo. The mass impinged on his ulnar nerve, which left him in agonizing pain and unable to move his left hand; it was bloated and looked like a fleshy blob. The assault on his left hand was particularly cruel.
When Jason was a kid—when we were kids together—Jason was a phenomenal athlete, cunning, tenacious, a slippery-quick southpaw. He wasn’t tall, but he sure could jump, an antelope with frog legs, all-state in Colorado in basketball and baseball. He had the looks to match, dark hair and dark eyes, a generous smile, his half-Italian, half-Jewish ancestry yielding an all-American mutt the girls couldn’t resist.
But to me, his defining characteristic was his laugh. It exploded at a high pitch bordering on soprano, often at one of his own jokes. It was sheer delight. Robert T. Hoff became an immune system marvel on Halloween night of 1977. He was dressed as a mummy. Born in 1948, raised in Iowa, son of an insurance man and a substitute teacher, he’d been in hiding since he was four. An Elegant Defense PDF Book
That was the first time he could remember that he and a boy next door fondled each other. He loved it, craved physical affection from other boys and eventually from men. He learned to hide the reality that for a few early years he dressed in his mom’s dresses and scarves. He overachieved in school.
He didn’t tell anybody about his passions after he made the mistake of doing so once, in seventh grade, and the kid he told, Steve Lyons, blabbed it. “I was referred to as a flaming faggot.” Bob needed a new strategy. He found it in imitation. There was a kid named Art who was the most popular guy in school. Bob learned to emulate Art. “I picked up on everything he did.
I picked out his extracurricular activities. I swam at the YMCA. I learned how to speak differently. There’s a gay accent, and I learned how to think in advance to not use a word that would contain a lisp. “Then I started to become popular, the star of the school play, elected president of the student government, the most popular kid in class.” An Elegant Defense PDF Book
He dated girls and stopped having sex with men until college, fearing he’d be ostracized. He went to law school and married a woman. He went on active duty in the Air Force. He and his wife tried to make it work. She didn’t want to be married to a homosexual. They divorced. He married again. At some point, Bob’s mother found out about his true proclivities.
They didn’t speak for twenty years because she thought him sinful. By 1977, Bob lived in Washington, D.C., now an accomplished lawyer —assistant general counsel for a major federal office, the General Services Administration. On October 31, Bob went alone to a party; his wife at the time, a flight attendant, part of the cover of his life, was out of town.
Bob wrapped himself in gauze he’d bought in a thirty-foot roll at Joann Fabrics and was hanging out at the party when he met John. John was a very fit redhead. Bob and John went upstairs and had unprotected sex. Two weeks later, Bob felt dizzy, lethargic, and tired, with achy flulike symptoms—not enough to keep him from work. The discomfort lasted ten days. An Elegant Defense PDF Book
“I chalked it up to the flu,” Bob recalled. Around Thanksgiving, Bob went to his cousin’s wedding in Cedar Falls. On the drive back, he felt really sick. He threw up and had diarrhea. He assumed he’d eaten bad shrimp. Bob, an overachiever all his life, went to see the doctor who had given him a physical when he applied for his private commercial flying license. Bob had hepatitis.
The version he had was hepatitis A, a strain that had been identified only a few years earlier, in 1973. It is an infection of the liver that takes some time to manifest. When it does, the symptoms that a person —in this case, Bob—experiences typically are those that come from the work that the immune system is doing when it fights back, inflammation.
For Bob, this diagnosis wasn’t such bad news, all things considered. If the immune system does its job properly, hepatitis A is a strain that can be overcome. In an immature B cell, the strands of V, D, and J material are in separate groupings, and they are separated by a relatively massive distance. An Elegant Defense PDF Book Download
But as the cell matures, a single, random copy of V remains, along with a single each of D and J, and all the other intervening material drops out. As I began to grasp this, it helped me to picture a line of genetic material stretching many miles. Suddenly, three random pieces step forward, and the rest drops away.
The combination of these genetic slices, grouped and condensed into a single cell, creates, by the power of math, trillions of different and virtually unique genetic codes. Or if you prefer a different metaphor, the body has randomly made hundreds of millions of different keys, or antibodies. Each fits a lock that is located on a pathogen.
Many of these antibodies are combined such that they are alien genetic material—at least to us—and their locks will never surface in the human body. Some may not exist in the entire universe. Our bodies have come stocked with keys to the rarest and even unimaginable locks, forms of evil the world has not yet seen, but someday might. An Elegant Defense PDF Book Download
In anticipation of threat from the unfathomable, our defenses evolved as infinity machines. “The discoveries of Tonegawa explain the genetic background allowing the enormous richness of variation among antibodies,” the Nobel Prize committee wrote in its award to him years later, in 1987.
“Beyond deeper knowledge of the basic structure of the immune system these discoveries will have importance in improving immunological therapy of different kinds, such as, for instance, the enforcement of vaccinations and inhibition of reactions during transplantation. Another area of importance is those diseases where the immune defense of the individual now attacks the body’s own tissues.
The so-called autoimmune diseases.” These last sentences—about autoimmunity and transplantation— introduced a central challenge to understanding our body’s defense: How does something so powerful avoid attacking the healthy parts of us? And how can we treat ourselves medically through things like transplants and medication without risking that. An Elegant Defense PDF Book Download
Our potent antibody system will reject anything that could actually help us, even if it seems alien at first? “They don’t harbor wimpy viruses,” Dr. Migueles said. He knew that they were seeing a powerful immune system variation. “This is evidence of what the human immune system is capable of doing.
They are alive with infection we thought uniformly fatal but acting as if they have the herpes virus, and the virus is sitting there doing very little.” There was a third key discovery. It now appeared that Bob and the other elite controllers had survived likely due to a very specific moment in the interaction between their immune systems and HIV: the first point of contact.
“The evidence is pointing us to what we call the prime—the priming event. It’s when the immune system first sees virus,” Dr. Migueles said. “We suspect people like Bob start down the road to being an elite controller right at the beginning.” These are major revelations, particularly the idea that the way you deal with a disease might well be dictated by this idea of a prime, or first point of contact. An Elegant Defense PDF Book Free
The initial response, whether to flu or HIV or a cold, might well echo through the immune system. The right first response could save your life, not that you have particular control over such a thing. However, knowing this can inform the way we build medicines, or study individuals to see their susceptibility to various viruses, say, through genetic testing.
Some of this is yet to be foretold by science—but is now within its grasp. Indeed, the sum of the work done at the NIH has led to a much deeper understanding of the immune system. Such essential science “has relevance for inflammatory-based disease, autoimmunity, and cancer,” Dr. Migueles said.
The papers the scientists have written are seeds of medicines and treatments and, in particular, of vaccine development. The way that elite controllers react is based on a “common pathway” of how our elegant defenses work on a molecular level. When someone smokes a cigarette, tiny little wounds are created inside the fragile pink tissue of the lung. An Elegant Defense PDF Book Free
Into the lungs pour several thousand chemicals, including a number of them that not only damage the DNA but that interfere with repair of DNA. Meanwhile, the police and fire brigade of the immune system shows up, and the process of wound healing begins. New cells are created. Over and over and over, cigarette after cigarette, year after year.
Smoking is a chronic activity, as opposed to, say, inhaling fewer chemicals less directly at the occasional campfire.) In the case of smoking, the malignant cells are fed and protected by the same system that cleaned out the wound in the first place and made sure that no pathogens were there to inflict harm. Some of those new cells are mistakes and are recognized as nonself.
And some have the right combination of random mutations to live and look a lot like self, so much so that the immune system, the very system created to defend us, becomes the promoter and protector of the tumor. Again, in key respects, cancer is just a numbers game. The more wounds you get, the more mutations and inflammatory events, the greater the likelihood of cancer. An Elegant Defense PDF Book Free
That’s what makes things like smoking so potent. The risks grow with each puff. Similarly, sun exposure, absent sunscreen, presents another opportunity for a wound and an inflammatory response, which, combined with mutations directly induced by UV irradiation, enhance the risk of the development of skin cancer, including the particularly dangerous melanoma.
Other toxins that come into the body, whether food toxins or chemical ones, can also create wounds, places of insult, even minor, that require repair, inflammation, rebuilding.