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The First Patented Animal Is Still Leading the Way on Cancer Research Oncomouse was a genetically engineered animal designed to help scientists learn more about tumors The online database categorizing collections of the Smithsonian Institution contained, as of a few weeks ago, 10,210,050 objects and documents, of which 230,590 (or around 2.25 percent) answered to the search term “mouse.” The holdings include carved-jade mice, (Mickey) Mouse yo-yos, mouse pads and the original Macintosh mouse. It also lists at least one actual, formerly living, mouse, of the laboratory, not house, variety. That would be the Oncomouse, an animal that made scientific and legal history as the first transgenic mammal to be the subject of a United States patent. The Oncomouse, engineered for the express purpose of developing tumors, was announced in a 1984 paper by Harvard researchers Philip Leder and Timothy Stewart and Paul Pattengale at the University of Southern California. Their efforts were intended to meet a need for animal models to study cancer in intact living organisms, rather than cell lines in petri dishes. To study cancer itself—how it forms and spreads in living tissue—and to test new treatments, required a standard animal that would develop tumors at a predictable, statistically significant rate. Leder and Stewart focused on breast cancer, for which there was a known causative agent in mice, the Mouse mammary tumor virus (MMTV), which can be transmitted in milk from mother to pup. By isolating the key DNA sequence from the virus and implanting it in embryos (along with, in varying combinations, the cancer-promoting oncogenes myc and ras), they created a mouse susceptible to breast cancer and other tumors: The predisposition could be inherited. In the next five years alone, the 1984 paper was cited more than 200 times in the scientific literature. Other labs were developing strains of malignancy-prone mice, using different genes. But Oncomouse was the first to be patented. In April 1988, patent #4,736,866 for “Transgenic Non-Human Mammals” was awarded to Harvard, which in turn licensed the patent to DuPont. (Another life-form, a bacterium, had been patented in 1981.) The chemical company had supported Leder and Stewart’s research and was now seeking a return. It promoted Oncomouse in ads and on T-shirts (the Smithsonian has one of those, too). This didn’t sit well with researchers accustomed to viewing lab mice as a shared (and inexpensive) resource. As MIT professor Fiona Murray wrote in a monograph (inevitably titled “The Oncomouse That Roared”), “The company set a high price per mouse although researchers had long-standing norms about freely trading mice.” Dupont “placed restrictions,” Murray continued, “on breeding programs, although this was considered a scientist’s prerogative. They demanded publication oversight....DuPont insisted upon a share of any commercial breakthroughs made using the Oncomouse.” The Oncomouse was also controversial in the context of animal rights. According to Kathleen Conlee of the Humane Society of the United States, the organization has “grave concerns about subjecting sentient animals to commercial utilization through genetic engineering. We also oppose the patenting of animals.” The Society advocates alternatives including computer modeling of disease. DuPont’s practices remained controversial among scientists until 1999, when Harold Varmus, head of the National Institutes of Health, brokered an agreement allowing scientists to use Oncomice without a fee for academic, noncommercial research. The Oncomouse, and similar strains of transgenic mice that followed, have been hailed as a revolutionary development in science. Leder, now retired, modestly describes their breakthrough as “a model system” that “provided evidence [for] today’s well-accepted concept that cancer is a genetic disorder.” In 1994—a decade or so after Oncomouse came squeaking into the world—the Smithsonian National Museum of American History acquired its specimen, preserved by freeze-drying, rather than taxidermy. The museum’s Mallory Warner believes this was done to keep intact the internal anatomy. “They were worried about maintaining preservation of tumors,” she says. “You can see lumpiness.” Today, the Oncomouse sits in a specimen box inside a storeroom. “It’s the only object [in our section] that our photographers asked to put up on Facebook,” she says. “This is one object everyone seems to get excited about.”

Director David Lynch Wants Schools to Teach Transcendental Meditation to Reduce Stress The acclaimed filmmaker has become the champion of the practice that's now been adopted by thousands of kids

Imagine the mind of David Lynch and you’ll likely picture a dark, surreal, wildly turbulent place. The 70-year-old filmmaker is world-renowned for movies like Mulholland Drive, a baffling erotic thriller, and Blue Velvet, which features a gas maskwearing sadist and a severed ear. Even Lynch’s network television show “Twin Peaks,” which was a cult hit in the 1990s (and will relaunch in 2017), had no shortage of violence, centering on a teenage prostitute who was murdered by a spirit called Killer Bob. In other words, Lynch might be the last person you’d expect to see promoting inner peace. But over the last decade, he’s spent much of his personal time and money helping low-income families, veterans, homeless people and other highstress groups learn Transcendental Meditation. This past year, the University of Chicago’s Crime Lab began a major multiyear study of Quiet Time, the David Lynch Foundation’s school meditation program. With 6,800 subjects in Chicago and New York, it’s one of the largest randomized controlled studies ever conducted on meditation for children. Lynch’s own childhood was fairly stress-free. He grew up partly in Boise, Idaho, where he spent his free time playing in mud puddles and watching ants climb up tree trunks. His parents nurtured his artistic talent. “It was as if there was just a foundation of love,” he reflects in David Lynch: The Art Life, a documentary that recently premiered at the Venice Film Festival. He became a serious painter in high school, and in his mid-20s, he received a grant to make his first film, Eraserhead. That’s when Lynch began struggling with anger and depression. He uses a very Lynchian metaphor to describe what it felt like: “a suffocating rubber clown suit of negativity.” It was 1973, a few years after the Beatles returned from their famous sojourn in Rishikesh, and Lynch’s younger sister suggested he follow their lead and learn Transcendental Meditation. The first time he meditated, he recalls, that oppressive second skin started to dissolve. “Down within I went,” he told me. “It was so beautiful, so profoundly beautiful. I said, ‘Where has this experience been?’” Lynch has meditated daily ever since, and in 2005, he created the David Lynch Foundation, which has sponsored meditation programs for half a million children in places as far-flung as Congo, South America and the West Bank. (Much of the money has come from fund-raising events headlined by stars like Katy Perry, Jerry Seinfeld, Louis C.K. and Sting.) The technique is different from mindfulness, an umbrella term that can describe anything from breathing to guided visualization to drawing exercises. People who learn TM (as I did at the age of 10) are given a mantra, or sound, and a specific technique for using it. You repeat the mantra and, if all goes well, your mind settles down into a deep, expansive silence. The fact that TM is a distinct technique, taught the same way everywhere, appealed to the University of Chicago Crime Lab. “This intervention has such simple ingredients,” says Aurelie Ouss, a postdoctoral fellow at the Crime Lab. “You just close your eyes and meditate.” The Crime Lab reviewed reports of reduced school violence and increased student happiness coming out of Quiet Time schools in New York, Detroit, San Francisco, Los Angeles and Washington, D.C. Still, even the most glowing anecdotes don’t qualify as solid evidence. “I’m not reflexively dismissive of touchy-feely or Kumbaya,” says Robert Pondiscio, a senior fellow at the Fordham Institute. “But there’s a tendency in education to take any kind of promising lead and very quickly turn it into orthodoxy.” He emphasizes the need for large sample sizes. “Schools have limitless moving parts,” he says. “Show me a randomized controlled study with thousands of students. Then all those other effects will work themselves out.” That’s what the Crime Lab is aiming to do. “We have a very high bar,” says Roseanna Ander, the Crime Lab’s founding executive director, who has worked on public safety programs with Chicago Mayor Rahm Emanuel and Illinois Gov. Bruce Rauner. “It’s part of our genetic makeup to be very skeptical.” To determine whether Quiet Time would work in Chicago classrooms, the researchers started with a pilot study of two schools. “If you spend time in these neighborhoods, you see that they’re on a par with the most dangerous places on the planet,” says Ander. “It’s hard to fathom how these kids can even go to school and learn anything.” There’s been plenty of research on how violence puts kids’ brains on high alert. A 2014 paper by the National Scientific Council on the Developing Child compares the overload of stress hormones to “revving a car engine for hours every day” and says it “increases the risk of stress-related physical and mental illness later in life.”

Studies on adults have linked TM practice with reduced stress-related problems such as strokes, heart attacks and high blood pressure, but it remains to be seen whether children will reap similar benefits. Over the next three years, the University of Chicago researchers will collect data on 6,800 public school students in Chicago and New York. Half will be randomly assigned to learn TM while the other half are told to do other quiet activities. The public school systems will track and share data, including the students’ grades, test scores, disciplinary incidents and police records. The Crime Lab researchers are also seeking approval to measure stress-related biomarkers such as cortisol levels. “If it works,” says Ouss, “we’ll learn something more general about how real the challenges of stress and violence can be.” For Lynch, reducing stress is only the first step. He wants to see today’s schoolchildren become artists and independent thinkers—perhaps even eccentric filmmakers in their own right. “Stress is like a vise grip on the creativity of young people,” he says. “Give them a tool to reduce their stress and wake up their brain, and there’s no limit to what they can create.”

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