Casale F.P.,European Bioinformatics Institute |
Rakitsch B.,European Bioinformatics Institute |
Lippert C.,Microsoft |
Lippert C.,Human Longevity |
Stegle O.,European Bioinformatics Institute
Nature Methods | Year: 2015
Set tests are a powerful approach for genome-wide association testing between groups of genetic variants and quantitative traits. We describe mtSet (http://github.com/PMBio/limix), a mixed-model approach that enables joint analysis across multiple correlated traits while accounting for population structure and relatedness. mtSet effectively combines the benefits of set tests with multi-trait modeling and is computationally efficient, enabling genetic analysis of large cohorts (up to 500,000 individuals) and multiple traits. © 2015 Nature America, Inc. All rights reserved. Source
Cook I.A.,Samueli Institute |
Espinoza R.,Human Longevity |
Leuchter A.F.,University of California at Los Angeles
Neurosurgery Clinics of North America | Year: 2014
Major depressive disorder is among the most disabling illnesses and, despite best practices with medication and psychotherapy, many patients remain ill even after several treatment trials. For many of these patients with treatment-resistant or pharmacoresistant depression, treatment with neuromodulation offers an alternative. Options range from systems that are implanted to others that are entirely noninvasive. This review surveys recent literature to update readers on 3 particular interventions: deep brain stimulation, transcranial magnetic stimulation, and trigeminal nerve stimulation. Additional comparative research is needed to delineate the relative advantages of these treatments, and how best to match individual patients to neuromodulation intervention. © 2014 Elsevier Inc. Source
A sign is seen at an AstraZeneca site in Macclesfield, central England May 19, 2014. REUTERS/Phil Noble CAMBRIDGE, England (Reuters) - AstraZeneca, working with genome pioneer Craig Venter, is launching a massive gene hunt in the most comprehensive bet yet by a pharmaceutical firm on the potential of genetic variations to unlock routes to new medicines. The initiative, announced on Friday, involves sequencing up to 2 million human genomes - the complete set of genetic code that acts as the software of life - including 500,000 DNA samples collected by AstraZeneca in global clinical trials. Financial details of the 10-year project were not disclosed but Mene Pangalos, head of early drug development, said the company would be investing "hundreds of millions of dollars". AstraZeneca aims to identify rare genetic mutations involved in every kind of disease by scanning DNA from volunteers who agreed to have their genomes sequenced and to provide access to detailed medical records. The project is made possible by a dramatic fall in the cost of genetic sequencing. It took government-funded scientists $3 billion and 13 years to sequence the first human genome by 2003. Today, it costs around $1,000 and takes just three days. AstraZeneca will work with Venter's U.S. company Human Longevity Inc (HLI), which will sequence the genomes, including 1 million from HLI's database, and use machine-learning software to find patterns in genetic variations. The British group, which is establishing an in-house Centre for Genomics Research in Cambridge, where it is relocating its global headquarters, has also partnered with the Wellcome Trust Sanger Institute and Finland's Institute for Molecular Medicine. AstraZeneca is not the first drugmaker to start amassing troves of human DNA in this way but Venter, one of the first scientists to sequence the human genome, said it was the biggest commitment to date by any pharmaceutical company. Regeneron Pharmaceuticals signed a deal with Pennsylvania's Geisinger Health System two years ago to sequence partial genomes of some 250,000 volunteers, while Roche's Genentech unit signed a deal last year for HLI to sequence tens of thousands of genomes. "The big thing here is the magnitude of what we are trying to do," Pangalos said. "This takes it to a completely different level and I think it is going to be relevant of every therapeutic area." Until now, the field of genomics has largely failed to live up to the hype of hoped-for medical breakthroughs, although more recently genetic understanding has been crucial in the development of some cancer treatments. Now, thanks to industrial-scale sequencing and advances in gene editing that allow scientists to quickly test the effects of genetic variations, progress is expected to accelerate. Venter believes it could also unleash a new era of forensics, with HLI trying to predict what people might look like from their DNA. AstraZeneca’s decision to embed genomics across its research and development follows a push last year by the company to expand gene testing into areas including heart disease and asthma. “I believe we really have finally turned the corner and genomics will become central in drug development efforts,” said David Goldstein, a genetics expert from Columbia University, who chairs AstraZeneca’s Genomics Advisory Board.
News Article | August 25, 2014
"The death by a thousand cuts applies to aging. So I am working to kill aging with a thousand cuts." During the dotcom boom, Dave Asprey made $6 million in one swoop. At the age of 26, in the rush of power and possibility that came with that sudden windfall of cash, he felt like nothing was beyond his reach, not even death. "I decided that I was just not going to die," he tells me, with a smile. "That would be my next challenge." And, so, Asprey joined the age-old fight to conquer death. Over the last 15 years, Asprey has been tinkering with technologies in the hopes of slowing the aging process in his own body. He describes this as bio-hacking, using the hacker mentality to turbocharge his own biochemistry. And to hear Asprey tell it, that's working: With a couple of scientific hacks, he’s lost hundreds of pounds, increased his IQ, and improved the quality of his sleep. All these things, he says, are also prolonging his life-span. He’s now sharing these techniques with others through Bulletproof Executive, the company he founded that creates coffee and other products to spike bodily performance, and as the chairman of the board of the Silicon Valley Health Institute, a group that meets monthly to discuss the latest developments in the study of longevity. The building that houses the SVHI, located just down the street from Google’s campus, is a microcosm of a growing Silicon Valley trend. There, Asprey and others are trying to stop individual bodies from aging—starting with their own—and investment is pouring into a growing number of companies whose stated goal is to increase human longevity and, in some cases, even cure death. Asprey freely admits that these are grandiose, quixotic endeavors. But in a place where geeks have changed the world with previously unthinkable breakthroughs in science, nothing seems impossible. "When you’re young and you’ve just created something amazing that makes you a ton of a money, you do egotistical things," Asprey says. "And I’m not saying that’s a bad thing: I want to swing for the fences. What is all of this cool technology we’re creating compared to getting an extra hundred years of life?" He's far from the only one dreaming of a home run. Last year Google launched Calico Labs, a medical company whose goal is to tackle aging and illness. While so far Calico is remaining fairly secretive about its projects (my requests for an interview were politely declined), experts believe its objective is to go beyond solving individual diseases the way most medical researchers have done until now. Instead, it will work on technologies that extend life through previously untapped means, like gene therapies and cryogenics. Earlier this year, Calico hired Cynthia Kenyon, an acclaimed geneticist from the University of California, San Francisco, who has been experimenting with tweaking genes in animals to slow aging. By disabling a gene called daf-2, she has doubled the life-span of roundworms, fruit flies, and mice. In her new role as VP of aging research at Calico, she will ostensibly be attempting to re-create these results in humans. This year, another company, Human Longevity, joined the anti-aging quest. Founded by J. Craig Venter, another millionaire entrepreneur, it’s central goal involves understanding DNA. Felix Frueh, the chief scientific officer of Human Longevity, explains that in some ways, the goals of Human Longevity are in line with what medicine has been trying to do all along: cure illness, improve life quality, and extend the human life-span. The difference is that his company applies big-data tools to process vast quantities of information we now have about the human body. The organization will sequence 2 million human genomes in five years, gathering unparalleled insights into the causes of disease. Rather than tackling problems incrementally, he says it is possible to work on a bigger scale, yielding more dramatic results. One of them could be cheating death. When I spoke to other members of the medical community—doctors and surgeons—they were largely skeptical about the anti-aging movement. Dr. Mark Shrime, a surgeon who serves as a clinical instructor at Harvard Medical School, says that radical life extension and curing death hardly ever comes up in hospitals or medical classes. He tells me that theories of longevity have been circulating for decades without any tangible results but outcomes seen in lab animals are rarely replicated on human bodies. "The question is, are these things feasible in high-level organisms, like primates," he says. Shrime points out that there is already an immortal jellyfish. "The steps to making humans immortal would be astronomical," he says. Dr. Raghu Athre at Memorial Hermann Northwest Hospital in Texas says that in working with patients, it becomes immediately apparent that human bodies are complicated and often react in ways that we could never expect. "Patients are not the same as test tubes and lab rats," he says. "There are so many variables that are out of our control." Athre argues that tech entrepreneurs are used to creating things they can control and work with data that makes sense; doctors, on the other hand, realize that human beings often defy logic. "While neck cancer is associated with smoking, there are also 29-year-old non-smokers who get neck cancer and die within six months," he says. This is not to say that doctors believe life extension will never happen. "We will probably get to a point where we know enough about aging to increase life-spans," Shrime says, "but if we are seeing breakthroughs in worms and jellyfish, this is still miles and miles away from anything tangible we can offer to patients." Many folks in Silicon Valley think differently. While no one is willing to give an exact schedule to when we will start seeing results in humans, startups tend to speak in five- to 10-year time frames. But if there is even a chance that immortality is just around the corner, the question inevitably becomes: Do we really want to double the human life-span? And if we could find a gene therapy that cured death altogether, would we actually want that? These are not questions that organically come up when speaking to anti-aging scientists and entrepreneurs. Among this Silicon Valley crowd, most feel that there is no question that life is worth preserving, perhaps forever. Yet, since so much of human life is built around mortality, extending life exponentially or eternally would effectively change the fabric of existence. If ever there was a time to get philosophical, now is it. John Troyer, a professor at the Centre for Death and Society at the University of Bath, has thought a lot about these issues. Troyer describes how conquering death has been an ongoing human fascination through history; thinkers have played with the idea in many ways. In Greek mythology, Tithonos was granted immortality but not eternal youth, so he lived forever, slowly losing his mind and strength, eventually begging for death. The Spanish myth of the fountain of youth asks whether it would be worth staying young forever when those around you age and die. The list goes on, and extends into many works of contemporary science fiction and fantasy, including a novel that will be released next week by bioethicist Kira Peikoff called No Time to Die, which follows a woman who stops aging after she turns 14. Peikoff has said she was inspired to write the book, in part, by an event that took place when she was 7 years old. Her father, the philosopher Leonard Peikoff, survived a heart attack, and Kira learned to greatly appreciate every new day. But living forever? That's another, fraught matter. "Let’s say curing death is possible, the question then becomes, is that actually desirable?" asks Troyer. "What kind of existence does that become?" Troyer argues that it is worth considering the potential consequences of Silicon Valley’s anti-aging projects. For instance, not everyone may want to live forever, for religious reasons or otherwise, so should people be allowed to refuse anti-aging treatments? Will they be seen as selfish, or even suicidal? There are also practical ramifications to think about: If the population keeps growing but life-spans double, how will natural resources be allocated? In 2003, the U.S. government wrestled with many of these questions. President George W. Bush convened a Council on Bioethics, which produced a report that included a chapter on ageless bodies, asking whether more people might choose to end their life in a world where people live exponentially longer. The report provided no answers, but its very existence says something about how near this immortal future might be. I brought many of these questions to Laura Deming, one of the youngest people in the anti-aging movement. She’s just 20, but she’s already been working on the problem for close to a decade. As a child, she remembers feeling intense sadness as she watched her elderly grandmother get tired and struggle to play with her. But while most children accept aging as a part of life, Deming decided that there must be a way around it. After all, she reckoned, many things seemed impossible to previous generations until a visionary decided to create it. Computers seem normal to us, for instance, but they were inconceivable 200 years ago. "I was taken by this idea that if you have a vision of what you want to make, you can just build it," she tells me. Deming immediately began trying to fix the problem. At 12 she started work at a lab and enrolled at MIT at the age of 14. Three years later, she dropped out to become a Thiel fellow to continue her research. She has recently started the Longevity Fund, a company that seeks to attract investors to startups working on aging and life extension. Although she’s devoted her entire life to defying aging, she understands the reasons other people might be ambivalent about her quest. "Death is so complicated because everybody has such different feelings about it," she tells me. "Some people want there to be death while others are scared of it: These views are hard to refute because they are so personal. Aging is innately important to us and sometimes, we’re not even sure we know why." However, Deming points out that people’s views tend to change when they move away from big existential questions to imagining individual people instead. While ending death is one part of the story, a more tangible part is curing the diseases that cause death. She believes almost everyone would cure cancer or arthritis or dementia if they could. As Deming surveys her chosen industry, she believes things are about to get more interesting. Calico and Human Longevity are now bastions in the field, and some of the smartest people in the world are working on these issues at the startups mushrooming in the Valley, some of which her company is aiming to fund. Still, I make the case that there must surely be a big difference between longevity and immortality. Even if it it turns out to be possible, defeating death must be very far off in the horizon. "It’s a lot closer than you might think," Deming tells me. "Extending life is already within our reach. In a couple of years, who knows what might be feasible?" ——————————- Update: This story has been changed based on Asprey's comment below about his office location.
News Article | January 15, 2015
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