Most students have a field they'd like to enter later in life. Describe the field you'd like to go into and discuss it's past and future.
Ancient Persian queen Atossa’s breast cancer was the tumor that launched a thousand ships. She could have been seen by any physician, from Babylonia to Greece, but she collapsed into a deep depression. Tightly wrapped in sheets, she didn’t want to see anyone. But a servant named Democedes convinced her to let him excise the searing tumor from her breast. There is no record of recurrence, but the reprieve from the pain was enough for Atossa to persuade her husband Darius to change his military campaign from eastern Scythia to western Greece. Atossa was deeply grateful to Democedes, and he wanted to return to his native Greece. Historian June Goodfield once wrote that “Cancer begins and ends with people. In the midst of scientific abstraction, it is sometimes possible to forget this one basic fact.” Medical oncology has undergone many transformations, from Galen’s theory of black bile to Halsted’s radical mastectomy pivoting to radical chemotherapy to genetically-based medicines like the breast cancer drug Herceptin. Medical, genetically-focused oncology has pushed the war on cancer farther than it has ever gone. Atossa’s war wasn’t just the literal war she convinced Darius to start; Atossa’s war represents a millennia-long struggle against this pantheon of malignancies. Every war starts with a battle plan. “The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease.” – Dr. Bert Vogelstein. The first hallmark of the disease is genomic instability. A specific mutation in an epithelial cell (usually in the p53 region) causes the cell to divide and reproduce at an uncontrollable rate, siphoning resources, and eventually metastasizing. It’s important to note that cancer is not caused by a single mutation, but an accumulation of mutations. But just as a cancer is not started by a single mutation, cancer is not a single disease. It is a broad landscape of deceptive mirages and deadly swamps. The only way out is through, and any strategic military campaign needs a map. The Cancer Genome Atlas (a collaboration between the National Institutes of Health and the National Human Genome Research Institute) aims to provide that. So far this research has revealed an average of eleven to fifteen genetic pathway mutations in each cancer cell. Some genes show up in multiple cancers; mountains in the landscape. As this genomic research continues, we will learn more about these mountains; replete with valleys and details specific to subtypes. For millennia, we have not understood what cancer is on the molecular level. Now we’re deciphering the recipe for the poison, ingredient by ingredient. As Sun Tzu wrote in the Art of War; “If you know the enemy and know yourself, you need not fear the result of a hundred battles.” The next ten years of medical oncology will have doctors who know more about Atossa’s old foe than any previous generation. Our battle map is more detailed than ever, but what new strategies will we use along with it? Precision medicine is the future of medical oncology. It specifically targets genetic pathways to destroy disease on the molecular level. To understand where the industry is going in ten years, first, we should look where it’s been. The story of the drug Herceptin is one of the early successes of genetic medicine. Herceptin works by targeting a specific subtype of breast cancer called Her-2. Dr. Siddhartha Mukherjee explains how it works: “Cancer cells that become habitually dependent on the activity of a gene for their growth can amplify that gene by making multiple copies of the gene in the chromosome. This phenomenon-like an addict feeding an addiction by ramping up the use of a drug is called oncogene amplification. Her-2, Slamon [a researcher studying] found, was highly amplified in breast cancer samples, but not in all breast cancers. Based on the pattern of staining, breast cancers could neatly be divided into Her-2 amplified and Her-2 unamplified samples-Her-2 positive and Her-2 negative.” Slamon’s discovery was important to another researcher at the pharmaceutical company Genentech, Axel Ullrich. Ullrich had one question following Slamon’s research. How could Her-2 activity be shut off? The answer to his question was an antibody. Antibodies are immunological proteins that bind to their targets with precise specificity. The immune system uses them regularly to fight normal infections. An antibody for the Her-2 gene would be a tracing missile against cancer. That’s exactly what Ullrich set out to find. His lab was able to synthesize an antibody to target the Her-2 variant of breast cancer. They sent it to Slamon’s lab at UCLA and a series of petri dish experiments revealed cancer cells that withered beneath the drug’s touch. Mouse trials came to the same conclusions. Soon, they synthesized it into a medicine for human patients. If cancer begins and ends with people, then the story of Barbara Bradfield is worth telling here. Barbara was sitting in her weekly Bible study class in 1991. Her pregnant daughter had been killed in a car accident a few months earlier. She was numb. Her Bible weighed on her lap and her fingers absentmindedly traced up along her neck. A fresh lump was there. Barbara’s breast cancer had relapsed and spread. A new round of tumors had clawed into her lungs as well. This was a death sentence, and Barbara knew it. She was offered more chemotherapy but decided against it. Instead, she pursued an herbal medicine program, bought a juicer, and booked a ticket to Mexico. Before she left, her oncologist had asked if he could send samples of her cancer to a distant lab in UCLA. She said yes; she had nothing to lose. Not long after, Dennis Slamon gave her a phone call. He wanted Barbara to join his clinical trial for a new drug, Herceptin. She said no. He called again and begged her to join. Barbara’s breast cancer had the highest amplification of Her-2 that Slamon had felt. After his second phone call, she said yes. Barbara joined the trial of fifteen women in August of 1992. They were all kept in the same room. The infusions and blood tests were tiring, yet the women developed a camaraderie. Some cracked jokes about cancer, some sat numbly in the lab, and one Chinese woman took ancient remedies alongside the cutting edge new medicine. But Barbara had something unique. The grape-sized lump in her neck became the litmus test for the trial to the women. After the infusions, they would lightly feel the lump, daring to hope it would shrink beneath Herceptin’s targeted assault. Two weeks after the treatment began, Barbara’s tumor had receded to the touch. A couple months later, CT scans validated what they had seen. Barbara’s lung tumors had shrunk, and the malignancy in her neck had all but disappeared. William Castle once described the fight against cancer, saying “Its palliation is a daily task, its cure a fervent hope.” For breast cancer patients with the Her-2 subtype, that hope is closer than ever before. But Herceptin is only the beginning. Our knowledge of cancer genes is only growing with the Genome Atlas. Precision medicine won’t stop at subtypes of cancers; it will continue to be tailored to the patients themselves. Let us return to the Persian queen, our heroine in oncology’s war on cancer. Where would a modern-day Atossa find herself as the industry continues to grow? The Journal of Clinical Oncology describes how medicine will change with precision medicine. Imagine Atossa, diagnosed with breast cancer on a warm Tuesday in 2027. Her oncologist lays out her plan; her tumor is excised and sent out for genomic sequencing. Atossa waits at home for her results, maybe having an extra martini to alleviate some stress. She takes an extra day off, unable to crawl out of bed. The sun rises on Monday morning, and Atossa gets an early phone call from the hospital. She walks into her doctor’s office and wipes her damp palms on her thighs. The oncologist flips open a manila folder and tells Atossa about the genome of her tumor. Turns out, her cancer isn’t rare. Three pharmaceutical companies have developed drugs for several of the key pathways in her cancer. The treacherous mountains in her malignancy have been mapped; a strategy to climb them has been drawn. The doctor flips the folder shut again with a quiet tap and hands her a treatment schedule. Atossa’s palms are dry. She leaves the doctor with the schedule and a lighter heart than when she walked in. Atossa’s war has been fought for four thousand years. The next ten years won’t defeat the pantheon. But thousands of patients will be saved by continuing the fight.
-2(-6-1-2) - (-2 + 7)
-2(-9)-(5) 18-5 Answer: 13
How do you build rapport with an audience while giving a presentation?
You should have consistent eye contact with the audience. Smiling and using hand gestures engages the audience with you. Last but not least, having a well-prepared speech is a final touch to build rapport with any audience.