New films from Oscar winners Barry Jenkins, Michael Moore and Steve McQueen will be unveiled as part of this years lineup
Much-anticipated new films from Barry Jenkins, Steve McQueen and Michael Moore are set to be unveiled at this years Toronto film festival, beginning this week.
In one of the festivals stronger lineups in recent years, there will be 138 world premieres featuring a long list of stars, including Judi Dench, Julia Roberts, Steve Carell, Colin Farrell, Robert Pattinson, Viola Davis and Kristen Stewart.
The Oscar-winning writer-director Barry Jenkins will debut the follow up to his best picture winner Moonlight, an adaptation of James Baldwins If Beale Street Could Talk. The 70s drama follows a couple torn apart by a false accusation of rape and stars newcomer Kiki Layne alongside Race star Stephan James and Emmy winner Regina King.
The 12 Years a Slave director Steve McQueen will be premiering his new star-studded crime thriller Widows, based on the Lynda La Plante miniseries with a script co-written by Gone Girl author Gillian Flynn. Viola Davis, Liam Neeson, Colin Farrell, Daniel Kaluuya, Jacki Weaver, Michelle Rodriguez and Robert Duvall all star.
Its a genre picture, McQueen said to Variety. I liked the idea of going into a genre, but still having social realism involved. Chicago had all the elements that I wanted to investigate, those of race, class, religion, policing Its such a fertile narrative environment. It has this criminality that goes all the way back to Al Capone.
Set to be one of the festivals most talked-about titles is Fahrenheit 11/9, the latest documentary from Michael Moore. Its a look at America under the presidency of Donald Trump, its title a reference to the day he was elected. My choir is the American people, Moore said to HuffPost. The old guard of the Democratic party has failed to speak to them. I will at least give them a song they can belt out.
Twenty years have passed since Harry Potter and the Sorcerer’s Stone was first released in the U.S., but Harry Potter fandom is as strong as ever. Potterheads have found many ways to express their love for the series, including tattoos, photo shoots, tribute bands and even baby names.
The Wizarding World is full of interesting names to inspire parents. Social Security Administration data shows that the franchise is already influencing American baby name choices, most notably with Luna. But the potential beyond that examples is endless.
We examined the books for some additional name inspiration. Here are more than 100 baby name ideas from Harry Potter characters ― the girls and the boys, the deceased and the living, the major and the minor, the good and the bad and the in-between.
The summer is almost over, and to distract myself from this deeply depressing fact, I will be losing myself in a good book and living vicariously through its characters. I already hit you guys with my summer reading list, so now it’s time for a back to school reading list. These are the best books you need to read before Labor Day. Okay, I know that’s kind of a tall order unless you’re a speed reader, so stock up on these for fall.
I loved Kara Thomas’ adult thriller, The Darkest Corners, so I was expecting a lot from her YA thriller, Cheerleaders. It did not disappoint. Cheerleaders is about a small-ish town in which five cheerleaders and friends all end up dead within the span of a few months. Two die in a car crash. Two are murdered. One commits suicide. Or did she? One of the cheerleaders’ younger sisters works to unravel the mystery surrounding these deaths that have plagued her town and her family.
If you read my summer reading list, you’d know I’m not really a big romance novel person but I loved Mr. Nice Guy. The book is about Lucas Callahan, a nice Southern gentleman from North Carolina, who moves to New York to pursue his dream of working at Empire magazine. There he meets Carmen Kelly, Empire’s notorious sex columnist… and has sex with her. Only, he doesn’t realize it’s her until she writes a not-so-favorable column about his performance, prompting Lucas to start a column of his own. It’s fun, it’s cute, and holy sh*t it is so refreshing to read a book about the publishing industry that ACTUALLY gets it totally right for once. (*Glares at The Bold Type which I know is not a book, but still*).
Sadie is one of the most anticipated YA thrillers of the year, and for damn good reason. Sadie follows a young girl who goes missing following her sister’s murder. But here’s the good part: it alternates between Sadie’s first-person narrative and the transcripts of a podcast that’s working to find Sadie. If you’ve ever wished Serial was a book, this is the next best thing—maybe even better.
F*cking duhhhh we’re putting our book on here. When’s Happy Hour? is the third Betches book, and as you may have guessed, it’s going to be about career advice. From crafting a resume to deliberating hooking up with the office hottie, we’re covering it all. Of course, with heavy doses of our signature snark. It doesn’t come out until October 23, so before you @ me in the comments, you should know this thing called preorder exists.
You know that quintessential icebreaker: if you could have dinner with five people, living or dead, who would you pick? That’s the central conceit to The Dinner List. Protagonist Sabrina invites her ex-boyfriend, estranged father, beloved professor, best friend, and oh yeah, Audrey Hepburn, to dinner. The result is a fun meandering through time that also touches profoundly on the many different types of love we feel for others.
I know this list is kind of heavy on the Young Adult thrillers, but you’re just going to have to deal. Young adults are the only ones actually going back to school right now, anyway. And in any case, this one is so good that you’re just going to have to read it. In this novel that combines mystery with the paranormal, five friends end up stuck in the “neverworld wake,” the place in between life and death, where they keep reliving the same day over and over until they can reach a unanimous vote on which one of them should live. Dun dun dunnnnn.
We’re moving out of the Young Adult genre into a book that is decidedly adult. I loved this book. Full stop. The writing was gorgeous—almost like prose poetry. I still think about some of the imagery Delia Owens used. The plot was equally interesting. Set in a North Carolina town, it follows Kya, the town’s “marsh girl” who’s raised herself in poverty in the swamps. Then, a prominent young man in the town is murdered, and there are many twists as the cops try to nail down a suspect. That’s all I’m gonna say.
Getting a little meta with the titles over here, but I promise it’s not on purpose. The Bucket List is about 25-year-old New York transplant Lacey Whitman, who learns that she has the BRCA-1 mutation. For those of you uninformed, it’s what Angelina Jolie had that led her to get a preventative double mastectomy. Lacey decides to do the same thing, but before she gets rid of her boobs, she makes a boob bucket list and tries to cross off everything. It’s sexy, it’s fun, it’s flirty—The Bucket List is overall a breezy read with a little bit more heart than your typical beach read.
These fun websites are great for when you, a human, are bored. They're also great for dogs.
Image: Darwin WiggetT/Getty Images
Bored with your usual digital stomping grounds?
Don’t fret, bored friend! There are plenty of sites other than Twitter or Instagram for you to waste countless hours on. Besides, it’s not like you could be doing something constructive at work or maybe, I don’t know, go outside. That requires like actually moving or interacting with other humans. Boo.
So if you prefer procrastination to productivity, this list of 50 websites should keep you amused for a few hours. Or you could sit there and keep refreshing Facebook until something interesting actually happens.
Blessed be the fruit. Honestly, we’re a little shocked that we’re having to put up posts about baby gifts, but here we are. Unfortunately for all of us, at some point we’ll have to attend a baby shower and watch a v pregnant almost-mom open gift after gift of everything from oversized stuffed animals to nipple balm. It’s a thing, and it’s terrifying.
Anyway, if you want to be the real VIP MVP of the baby shower circuit, make sure your gifts are on point. Whether you shower the parents-to-be with amazingly hilar onesies or gift cards to the best area restaurants ensuring them a night out, don’t fall into the trap of getting boring, loud, or weird baby gifts.
I’m not going to NOT plug our own merch, which is like, rly cute. You may as well buy about 100 onesies for any new child, since they’re likely to go through anywhere from five to 500 in any given day. They may as well look cute while they throw up on themselves. Babies, they’re just like us.
Mama is going to get a sh*tload of stuff for baby, i.e. toys, diapers, more diapers, onesies, baby food puree systems, tiny shoes and socks, etc. Get something for the new mom to enjoy, like, a day trip to a really nice spa complete with an offer of babysitting (I KNOW), several bottles of wine that age well considering she won’t be able to drink it until she’s done breastfeeding (unless she pumps and dumps), or a foot massage system that she can sit in while ordering her SO to actually change a diaper for once.
If mom is already the owner of something like a Vitamix or Ninja blender system, she’s probably going to love the Baby Bullet (kinda off on the name, there, marketing people) or a similar product. It allows mom to make her own concoctions of baby food. That means she doesn’t have to run to the store and buy 1,000 glass jars.
You know what new parents don’t want? Any kind of toy/distraction device that sings a song or makes any kind of sound. They’re getting enough sounds every three hours, morning, noon, and night. Find a toy that makes no noise but will keep bae distracted so mom can, like, pour a glass of wine for herself. Try items made from fabric, like soft baby books, foam blocks, and other soft, soothing, items.
Call it bougie, and it is, but if this is mama’s first baby, you can’t go wrong by buying the classic silver baby spoon from Tiffany’s. This isn’t really something that serves a true purpose–it’s a keepsake. Tiffany’s also has baby brushes, rattles, and other silver things that, at the price of around $300+, will definitely get you into the good graces of the parents … hopefully, so much so, that they’ll never ask you to babysit. It’s a win-win for everyone, fam.
This is neither classy nor cute, but the parents-to-be will be singing your praises. If there’s one thing that babies go through a lot of, it’s diapers. Duh. Build a diaper pyramid with about 15 packages of Pampers or Huggies or whatever, and the parents will be forever grateful. You’re essentially saving them a screaming argument at 3am about whose turn it is to do a diaper run. Praise be.
Hey, you know what’s awesome? Being able to tune into baby in the crib without leaving the comfort of the couch. These days, there are tons of systems that include full sound AND video, so mom or dad can watch bae sleep (not in a creepy way) and decide whether or not the fussing is worth getting up for.
The First Minister Carwyn Jones described Thomas’s success as a “fantastic achievement”.
“Wales will be cheering you on as you head to the finish,” he tweeted.
Welsh Secretary Alun Cairns described the 32-year-old as an inspirational role model, adding: “His grit and determination over the last few weeks demonstrates how much he wants to win this epic race.
“Geraint is a brilliant ambassador for the sport, for Wales and thoroughly deserves his place in history – llongyfarchiadau mawr.”
Huw Jones-Williams, head teacher at Whitchurch High School. said: “It is amazing to see that one of our former students has won the Tour de France and become the first Welshman to do so.
“Geraint is already a legend at the school being a triple World Champion, double Olympic gold medallist and Commonwealth gold medallist amongst his many incredible achievements.”
Thomas, a two-time Olympic Gold medallist, sets off on his final leg of the journey on Sunday afternoon, finishing in the Champs-Elysees at about 18:00 BST.
As long as he crosses the finish line, he will win the race.
He described Saturday’s penultimate stage as “insane”.
He was greeted at the finish line by his wife Sara, who had been secretly flown out for the occasion.
“I tried not to think about it, just take it day by day. I’ve won the Tour de France man, I don’t know what to say,” he said after crossing the line almost two minutes ahead of his nearest rival, Tom Domoulin.
“The last time I cried was when I got married and I don’t know what’s happened to me.”
Libraries are amazing and bad takes in Forbes are not.
Image: Mark Lennihan/AP/REX/Shutterstock
UPDATE: July 23, 2018, 1:48 p.m. EDT As of Monday afternoon, it appears as if the story has been pulled from Forbes without a note or any other reason. The story has also been removed from Mourdoukoutas’ author page. I’ve reached out to Forbes for details but, for now, you can read a cached version of the story here and an updated version that was briefly on the site is here (via Wonkette).
There are bad takes, and then there’s the take by Forbes contributor Panos Mourdoukoutas (who also serves as Chair of the Department of Economics at Long Island University) that local libraries should be replaced by Amazon book stores.
Among the reasons Mourdoukoutas offers are: libraries don’t have as many public events as they used to because of school auditoriums; people go to places like Starbucks to hang out and work and read now instead of their library; and because technology makes physical books obsolete.
These arguments are easy to rebut. School auditoriums are hardly new and libraries remain bedrocks of local communities, Starbucks locations don’t offer free loans of books, and libraries all over the country have amassed huge ebook collections, meaning you can still check out books in whatever format you want for free, which is way cheaper than any price on Amazon.
Also, since Mourdoukoutas brings up the demise of video rental places for some reason, it’s worth pointing out that plenty of libraries now offer streaming audio and video services. And many larger libraries, including New York City and Chicago, loan you free museum passes using your library card, proving they’re still mighty useful to the community.
It’s a poorly written and barely defended take. The one cogent argument Mourdoukoutas does make is that such a move would save residents in tax dollars and would help Amazon stock holders. Because apparently being the richest man in modern history isn’t enough for Jeff Bezos and harming lower-income communities where residents rely on libraries as their primary source for books and more is totally fine.
Historically those with power overtly protected their position by keeping oppressed communities illiterate. This idea is a modern reincarnation. Libraries serve POC, the poor, etc. They are where people apply for citizenship, register to vote, access social programs. https://t.co/4BGS3yhorz
I worked at a library. They are a community-facing center of PUBLIC GOOD, bridging the people with information and entertainment. Librarians are BOOK WIZARDS and reference librarians are INFOSORCERERS and we must protect libraries as a precious resource.
The elitist ignorance here is staggering. Public libraries are refuge – from, among many other things, the spread of corporate monolith advocated in this piece. Please let the response be a tripling down of commitment to preserve free community spaces. https://t.co/IZbGmPGFHn
Nir Barzilai has a plan. It’s a really big plan that might one day change medicine and health care as we know it. Its promise: extending our years of healthy, disease-free living by decades.
And Barzilai knows about the science of aging. He is, after all, the director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx. And, as such, he usually talks about his plan with the caution of a seasoned researcher. Usually. Truth is, Barzilai is known among his colleagues for his excitability—one author says he could pass as the older brother of Austin Powers—and sometimes he can’t help himself. Like the time he referred to his plan—which, among other things, would demonstrate that human aging can be slowed with a cheap pill—as “history-making.” In 2015, he stood outside of the offices of the Food and Drug Administration, flanked by a number of distinguished researchers on aging, and likened the plan to a journey to “the promised land.”
Last spring, Barzilai traveled to the Vatican to discuss the plan at a conference on cellular therapies. It was the second time he’d been invited to the conference, which is a pretty big deal in the medical world. At the last one, in 2013, he appeared alongside a dwarf from Ecuador, a member of a community of dwarfs whose near immunity to diabetes and cancer has attracted the keen interest of researchers. The 2016 conference featured a number of the world’s top cancer scientists and included addresses from Pope Francis and Joe Biden. That Barzilai was invited was a sign not only of his prominence in his field but also of how far aging research, once relegated to the periphery of mainstream science, has come in recent years.
That progress has been spurred by huge investments from Silicon Valley titans, including Google’s Sergey Brin and Larry Page, Amazon’s Jeff Bezos, PayPal cofounder Peter Thiel, and Oracle cofounder Larry Ellison. Armed with such riches, biotech researchers are now dreaming up a growing list of cribbed-from-science-fiction therapies to beat back death: growing new organs from your own DNA, infusing older bodies with blood and stem cells from young bodies, uploading brains to computers.
Almost nothing seems too far-fetched in the so-called life-extension community. And yet, while it’s certainly possible that this work will lead to a breakthrough that will benefit all of humanity, it’s hard to escape the sense that Silicon Valley’s newfound urge to postpone aging indefinitely is, first and foremost, an attempt by the super wealthy to extend their own lives. As one scientist recently put it to The New Yorker, the antiaging science being done at Google-backed Calico Labs is “as self-serving as the Medici building a Renaissance chapel in Italy, but with a little extra Silicon Valley narcissism thrown in.”
Barzilai’s big plan isn’t necessarily less quixotic than those being dreamed up at Silicon Valley biotechs. It’s just quixotic in a completely different way. Rather than trying to develop a wildly expensive, highly speculative therapy that will likely only benefit the billionaire-demigod set, Barzilai wants to convince the FDA to put its seal of approval on an antiaging drug for the rest of us: A cheap, generic, demonstrably safe pharmaceutical that has already shown, in a host of preliminary studies, that it may be able to help stave off many of the worst parts of growing old. Not only that, it would also shorten the duration of those awful parts. (“How To Die Young at a Very Old Age” was the title of his 2014 talk at TEDx Gramercy in New York City.)
The drug in question, metformin, costs about five cents a pill. It’s a slightly modified version of a compound that was discovered in a plant, Galega officinalis. The plant, also known as French lilac and goat’s rue, is hardly the stuff of cutting-edge science. Physicians have been prescribing it as an herbal remedy for centuries. In 1640, the great English herbalist John Parkinson wrote about goat’s rue in his life’s work, Theatrum Botanicum, recommending it for “the bitings or stings of any venomous creature,” “the plague,” “measells,” “small pocks,” and “wormes in children,” among other conditions.
According to some sources, goat’s rue was also a centuries-old remedy for frequent urination, now known to be a telltale sign of diabetes. Today, metformin, which helps keep blood sugar levels in check without serious side effects, is typically the first-choice treatment for type 2 diabetics, and it’s sometimes prescribed for prediabetes as well. Together, the two conditions afflict half of American adults. In 2014 alone, Americans filled 76.9 million prescriptions for metformin, and some of those prescriptions went to Barzilai himself. (He’s been taking the drug since he was diagnosed with prediabetes around six years ago.)
A native Israeli, Barzilai speaks English with an accent, never letting grammatical slipups slow him down. He has short, boyish bangs and a slightly rounded face. His thick glasses and natural exuberance give him the look of an actor typecast as an eccentric researcher. He traces his interest in aging to the Sabbath walks he took with his grandfather as a child. Barzilai could never quite reconcile the frailty of the old man with his grandfather’s stories of draining swamps in prestate Israel. “I was looking and saying, ‘This guy? This old guy could do that?’”
Barzilai first studied metformin in the late 1980s while doing a fellowship at Yale, never imagining the drug would later become his focus. When the FDA approved it as a diabetes treatment in 1994, there was little reason to think it would someday become one of the hottest topics in medicine. But in the following two decades, researchers started comparing the health of diabetics on metformin to those taking other diabetes drugs.
What they discovered was striking: The metformin-takers tended to be healthier in all sorts of ways. They lived longer and had fewer cardiovascular events, and in at least some studies they were less likely to suffer from dementia and Alzheimer’s. Most surprising of all, they seemed to get cancer far less frequently—as much as 25 to 40 percent less than diabetics taking two other popular medications. When they did get cancer, they tended to outlive diabetics with cancer who were taking other medications.
As Lewis Cantley, the director of the Cancer Center at Weill Cornell Medicine, once put it, “Metformin may have already saved more people from cancer deaths than any drug in history.” Nobel laureate James Watson (of DNA-structure fame), who takes metformin off-label for cancer prevention, once suggested that the drug appeared to be “our only real clue into the business” of fighting the disease.
The more researchers learn about metformin, the more it can seem like a medieval wonder drug poised for a 21st century resurgence. In addition to exploring its potential to help treat the most common afflictions of aging, researchers are now also investigating whether metformin might improve symptoms of autoimmune disorders, tuberculosis, and erectile dysfunction, among other conditions. And while much of this research is still in its early stages and may fizzle, metformin is already prescribed off-label to treat obesity, polycystic ovarian syndrome, infertility, nonalcoholic fatty liver disease, and acne—not bad for a plant that the USDA officially lists as a noxious weed.
Barzilai, like most in his field, was aware of the good news about metformin that had been trickling out year after year. But the true origins of his big plan have less to do with metformin itself than with a convergence of a number of different strands of aging research. The first breakthroughs came in the ’90s, when researchers demonstrated that a single mutation in a microscopic worm could double its lifespan. Among the takeaways: The aging process might not be as hopelessly complex as it had previously seemed. As this new understanding of aging was settling in, Barzilai was beginning a series of studies on people who live to unusually old ages—“superagers,” as Barzilai calls them.
In the course of that work, he began to notice a pattern that other researchers had also seen: The superagers died from the same diseases as everyone else, but they developed them years later and, critically, closer to the ends of their lives. In other words, if you could slow the aging process, you might do more than give someone a few more years. You could also be able to shrink the suffering and enormous expense that accompanies cancer, heart disease, dementia, and all the other plagues of growing old.
The true promise of antiaging drugs, Barzilai and his colleagues came to think, wasn’t immortality. The ideal drug might not even extend life for all that long. Instead, it would extend what Barzilai and his colleagues call our health span—the years of healthy, disease-free living before the diseases of aging set in. S. Jay Olshansky, a professor at the School of Public Health at the University of Illinois at Chicago, is advising a small team of researchers who are working with Barzilai on a new study of metformin’s antiaging properties. He believes that even a modest slowing of the aging process—and the subsequent extension of health span—would have a greater impact on health and quality of life than a cure for cancer. The upshot: a multitrillion-dollar economic benefit in the decades ahead.
In 2013, Barzilai and two other researchers received a small grant from the National Institute on Aging to explore how the field might move forward. That grant, in turn, led to a 2014 conference in the Spanish countryside, where several dozen researchers gathered in a medieval castle turned hotel to map out a path forward. The castle, surrounded by ancient stone walls and towers, was the sort of place where goat’s rue may have once been handed out by local herbalists. Barzilai describes it as a “Spanish prison.” But the isolation of the setting turned out to be a good thing. “We were stuck in this place with one another,” says Steven Austad, a researcher at the University of Alabama. “It was really quite intense.”
The assembled scientists and academics focused on one obstacle above all: the Food and Drug Administration. The agency does not recognize aging as a medical condition, meaning a drug cannot be approved to treat it. And even if the FDA were to acknowledge that aging is a condition worthy of targeting, there would still be the question of how to demonstrate that aging had, in fact, been slowed—a particularly difficult question considering that there are no universally agreed-on markers. What they needed, Barzilai and the others concluded, was a precedent-setting test case—a single study that would change the rules forever, not unlike how trial lawyers search for a perfect plaintiff when they’re going to the Supreme Court to set a new legal precedent.
Which drug to use for this precedent-setting case was less obvious. Austad was among those who favored a drug called rapamycin, which has been shown to outperform metformin in studies of longevity in animals. But Barzilai was concerned about rapamycin’s powerful side effects. (An immunosuppressant, it raises the risk of opportunistic infections.) “One thing I don’t want to do is to kill anyone,” Barzilai tells me.
He was confident that metformin was good enough for the job. He has maintained this confidence ever since he read a 2014 study that reviewed the fate of 90,400 type 2 diabetics taking either metformin or another medication. The metformin patients in the study not only outlived the diabetics taking the other drug—a not especially surprising result if metformin is a superior treatment—but also outlived the nondiabetics studied as a comparison.
In the end, the scientists holed up in the Spanish prison settled on an unusual clinical trial designed to test whether metformin can, in addition to extending life, delay the onset of cancer, cardiovascular disease, and cognitive impairment. The FDA will not make its decision on whether metformin becomes the US’s first antiaging drug until the study, dubbed Targeting Aging with Metformin (TAME for short), is complete. That won’t happen for at least another five years. But, based on their June 2015 meeting with FDA officials, Barzilai and his colleagues are optimistic that the FDA is onboard. “Within five minutes, we were all in complete agreement that this is plausible” and “a good idea,” S. Jay Olshansky says.
Barzilai was not scheduled to speak until the third and final day of the Vatican conference. So for the first two days he busied himself mingling with other conference attendees, often approaching them and lifting the IDs hanging from their necks up to his face so that he could make out their names. One night, he turned to an elderly woman in his hotel elevator and asked how old she was, something he often does out of professional interest. Regardless of what number these women offer up, Barzilai always tell them they are, in fact, biologically younger. When Barzilai and the woman got off on the same floor of the hotel, he took her hand and led her in a little dance. “My continuous mitzvah project is to dance with elderly women,” he tells me, using the Hebrew word for “good deed.”
When it was finally his turn to address the conference, Barzilai began by pointing out that the likelihood of being diagnosed with a deadly chronic disease, such as cancer, heart disease, or Alzheimer’s, increases dramatically as we age. The current approach of treating each illness separately, he suggested, ultimately amounts to a fool’s errand. We survive cancer only to get heart disease a few years later, or vice versa. “Unless we target aging itself,” he announced, “all we can hope is that we switch one disease for another.”
If and when the FDA approves the first antiaging drug, Barzilai believes it will create a domino effect of health and economic benefits: Insurance companies will begin to cover antiaging drugs, and pharmaceutical companies, in turn, will begin investing more in antiaging research and produce new and better drugs that extend human health span. Whether all these benefits will come to pass is hard to know. Big Pharma’s hesitancy to dive into antiaging drugs may have as much to do with past failures as the FDA. In 2008, GlaxoSmithKline spent $720 million on a biotech company that many believed would develop antiaging drugs from resveratrol, a compound found in red-wine grapes. Five years later, after a series of failed trials, the company killed the initiative.
Thus far, getting the FDA excited about TAME has proven to be less challenging than convincing someone to pay for the study. Because metformin is a generic, there is no pot of gold waiting for investors at the end of the process. The TAME trial, which will enroll approximately 3,000 men and women between the ages of 65 and 79 at 14 centers across the country, is projected to cost $69 million. Barzilai is counting on the National Institutes of Health to cover a significant share of the cost, and he has been directly involved in lobbying the agency to back the study. (When he met with Mississippi senator Thad Cochran, he joked that Mississippians need a drug like metformin because they are victims of the state’s great food and can’t stop eating.)
The rest of the money will need to come from private donations. Barzilai recently told me that a billionaire, who insists on remaining anonymous, is considering matching the NIH funding. But, for now, Barzilai still has little to show in the way of locked-down TAME funding beyond the money that he, his wife, and his in-laws have given to the American Federation for Aging Research, the organization sponsoring the trial. “Rich people are interested in aging,” he says. “They call me to prescribe metformin, but they don’t understand that I’m doing something that’s more profound.”
But if the antiaging gurus aren’t ready to pour their millions into a metformin study just yet, that doesn’t mean they’re not interested in the drug. Another member of the aging panel at the Vatican, Robert Hariri, cofounder and president of genetic sequencing pioneer Craig Venter’s Human Longevity Cellular Therapeutics, noted during the discussion that he takes metformin (he claims that it has improved his eyesight), as do Ray Kurzweil, of Singularity fame, and Ned David, cofounder of Silicon Valley startup Unity Biotechnology, which is developing its own antiaging drugs.
In his recent book Tools of Titans, Silicon Valley self-help guru Tim Ferriss introduces readers to “billionaires, icons, and world-class performers” so that the rest of us might discover the secrets of their success. Ferriss estimates that a dozen of the people featured in the book take metformin. The problem is that “metformin is available” already, Barzilai told me. “The wealthy donors “want to concentrate on the next one that will allow them to live forever.”
With so many potential uses, it can be difficult to avoid the conclusion that metformin is too good to be true, and some of the hype may yet prove to be overblown. Many of the most exciting cancer findings linked to the drug, for instance, come from observational studies of diabetics. They show a correlation between metformin and lower cancer rates, but don’t prove that the compound is responsible for those outcomes or that they extend to nondiabetics. It’s possible that, rather than metformin lowering cancer risk, the other diabetes medications are increasing it.
It’s also possible that, as some metformin skeptics have argued, a lack of statistical rigor has exaggerated some of the most sensational cancer findings. And while evidence from observational studies of cancer patients has been supported by animal experiments as well as by human trials that measure markers of cancer, when it comes to the most important test of a cancer treatment—whether a drug actually extends life—metformin has thus far been a bust. In two controlled trials involving patients with advanced pancreatic cancer, a notoriously difficult cancer to treat, metformin failed to provide any benefit.
But while it’s possible that metformin won’t live up to the excitement it has generated, it’s also possible that the compound, or a very closely related one, may turn out to be even more promising than the current scientific literature suggests. Because it’s no longer under patent, metformin is widely studied, and yet, for the same reason, it doesn’t benefit from the rigorous (and expensive) multistage pharmaceutical drug development process that could determine the most effective dose for cancer or which patients are most likely to respond to treatment. “I don’t think the trials have been done in a very rational way,” says Navdeep S. Chandel, a metabolism researcher at Northwestern University who studies metformin. “The antidiabetic dose that you give to patients might not be enough metformin” for cancer.
If researchers don’t yet know the best way to treat cancer with metformin, they are making real progress on the long-standing question of how it works inside our cells. After a patient takes a metformin tablet, much of the drug ends up in the liver, where it disrupts the process by which cells break down and burn nutrients with oxygen for energy.
If metformin shut down the oxygen reactions completely, it would be deadly—that’s how cyanide works. But the drug merely interferes with one stage of the multistage process by which the energy from nutrients makes its way to oxygen. Michael Pollak, a cancer researcher at McGill University who has studied metformin, compares it to water that’s sprinkled on flames—the fire slows down but doesn’t get extinguished.
It’s possible that metformin treats cancer and other conditions directly by interfering with energy production and, in the process, reducing inflammation. But the cascade of metabolic changes that follow may be even more important. When liver cells are in a state of energy stress, they begin sending out less glucose. “If you’re running out of energy yourself, you don’t want to give it to the rest of your body,” Pollak says.
Lower glucose, in turn, means that the pancreas needs to send out less insulin, the hormone that tells cells to take up and store nutrients. And it’s this indirect influence on insulin that many researchers now point to as a possible explanation for many of metformin’s remarkable range of benefits. Too much insulin has been linked to almost every condition metformin appears to treat, including aging.
The biological logic of the link among glucose, insulin, and aging wasn’t hard for researchers to unravel. Insulin sends a message to our cells that nutrients are available, meaning it’s time to grow and proliferate. When the levels of the hormones drop, it’s a signal to cells that its time to enter a life-extending mode of conservation. Such a system makes evolutionary sense. It would have allowed an organism to survive periods of food scarcity with the hope of reproducing when better times arrived. It could also explain why very low-calorie diets can significantly extend life in animals. Metformin is often said to mimic the effects of a low-calorie diet—a pill that offers the benefits of eating less, without leaving you hungry.
Aging in humans is considerably more complicated than aging in microscopic worms and other model organisms, including fruit flies and mice. But evolution builds on what comes before, and the mechanisms have fundamental similarities across species. “Cancer in each individual is a different and specific disease. The genome of the cancer is different,” Barzilai says. “A lot of aging is the same in yeasts and in flies and in nematodes and in mice and in rats and in humans.” Barzilai’s English begins to falter under the weight of his enthusiasm. “We’re not going to prevent every disease in the world,” he says. But we can target “this risk factor of aging that is so important, and take it out of the table.”
When Barzilai’s Vatican panel ended, the conference paused for a scheduled break and the attendees surged forward to ask him about metformin. He told a man in an expensive-looking suit that if he didn’t want to pay $20 a month in the US, he could get metformin for $2 a month in Mexico. When another man asked Barzilai what dosage he should take, Barzilai turned to the woman by his side and asked her how much longer she wanted him to remain alive.
Barzilai seemed entirely in his element as he whizzed around the room, shaking hands and cracking jokes. But when it was just the two of us, he looked momentarily deflated. I asked him what was wrong. He told me that the moderator had cut the session short before he’d had a chance to mention the most important thing about his plan to change health care with his groundbreaking metformin study: “I wanted to say what it costs, and ask if somebody here is ready to fund it.”
Sam Apple (@samuelapple) teaches science writing at the University of Pennsylvania. He is working on a book about cancer and nutrition.
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If you spent any time on social media this past weekend, you no doubt saw hundreds — nay, thousands — of people reflecting on the recent suicides of Kate Spade and Anthony Bourdain. Some wondered what could have motivated these two wildly successful people to take their own lives. Others noted that we can never know someone else’s pain — and that, in any case, just because someone leads a seemingly blessed life doesn’t mean she or he can’t suffer from depression.
The New York Times tweeted out helpful recommendations of books that explored depression, including Andrew Solomon’s classic, “The Noonday Demon.”
Three books that explore what leads to suicide, and the tolls of depression and emotional pain.https://t.co/V0GePiW3zP
Lots of suggestions were offered to help people suffering from depression:
Not everyone who is suffering has the ability to reach out for help. So if you’re not suffering from depression, YOU reach out. I was fortunate enough to have such a person in my life many years ago. She saved my life. You could be that person to your loved ones. (1800)-273-8255
And then there was the category that hit me the hardest: people who had suffered from depression and decided that now was the right time to tell their own stories. Peter Sagal, the host of NPR’s comedy quiz show, “Wait, Wait, Don’t Tell Me,” was one such person; Kirsten Powers, a USA Today columnist, was another. Both hinted that in their darkest days, they had harbored thoughts of suicide.
Such stories — or rather the accumulation of such stories — convey a brutal truth: Depression is far more commonplace than you might think. And people you would never expect to suffer from depression — hey, doesn’t Sagal tell jokes for a living? — do.
These stories also speak to the stigma that still attaches to depression. Untreated depression can cost people their marriages, their jobs, their friends — and yes, their lives. Yet far too often, people who suffer from depression are afraid to acknowledge it, out of fear or shame.
The decision to come out of the depression closet usually comes after a great deal of hesitation — and as part of a conscious effort to say out loud that depression is a medical condition, not a character flaw. Stigmatizing it isn’t just counterproductive, it’s dangerous.
I know these feelings because I’ve had them myself over the last few years, as I’ve gone back and forth over whether to tell my own story of depression. Like those others who have come forth after the deaths of Spade and Bourdain, my answer — finally — is yes. So here goes.
Twelve years ago, when I was 54 and living a seemingly blessed life, I decided to get divorced. That decision, though the right one for me, consumed me with guilt, and caused me to spiral into a paralyzing depression, something I had never experienced before. I lost all interest in everything; my brain became a never-ending loop of crazed and dark thoughts. I could barely get out of bed. My work, which had always been so central to my life, felt meaningless. At Thanksgiving that year, I was so paralyzed I could barely speak to my own children. It was the only time in my life that I had suicidal impulses.
I got through that first depression with the help of a new psychologist, some anxiety medication, and my soon-to-be ex-wife, who despite everything helped coaxed me back to health. Because depression had never been part of my makeup, my working assumption was that it was a one-off. It was the result, I assumed, of my being traumatized at the thought of divorcing a good person with whom I had raised three children and had shared a life for over 30 years.
But I was wrong. Somehow that episode triggered something, or changed something, in my brain. Three years later, I had a second bout of depression. And then a third a few years after that. And a fourth. In between I would have long stretches of normalcy, as well as shorter stretches of what I now realize was mild mania — hypomania, it’s called — during which I would feel invincible. Deep into middle age, I had become bipolar.
Except that I resisted that diagnosis with every fiber of my being. Partly it was because I was terrified at the idea of having to take lithium, the drug of choice for people with bipolar disorder. (Didn’t it have side effects that caused patients to stop taking it?) But it was also because I was ashamed. Why? I can’t really say. But that feeling was real, and it was powerful.
Because these subsequent depressions were not as severe as the first, I decided to push through them. I went to work as if nothing were wrong, and managed, somehow, to write two op-ed columns a week for the New York Times, where I was employed at the time. But my thinking was impaired, and I sometimes blurted out non sequiturs during interviews, which did not enhance my ability to get the information I was seeking. I would spin my wheels for days at time, unable to come up with a column idea until the last possible second, which put me under the kind of deadline pressure that does not make for good writing or good thinking.
Worst of all, as a direct consequence of being depressed, I made several major factual errors that required substantial corrections in the paper and apologies from me. These mistakes didn’t just discredit me, they also, painfully, embarrassed the Times editorial page. In no small part because of those errors, my boss — who had no idea I suffered from depression — eventually had me shipped off to the sports section.
My most recent bout of depression came two years ago. This time I decided to acknowledge to the sports editor that I was depressed, though I assumed I would try to push through it once again. But I was acting erratically in the office, and to his everlasting credit, he wasn’t willing to look the other way. He insisted that I go on sick leave so that I could get better at home, with the help of my family and without the pressures of work.
Which I did. That was the summer when I finally accepted that I had become bipolar in midlife, agreed to let my doctor prescribe lithium, and began telling friends that I suffered from depression. When I returned to the office after a two month leave and colleagues asked me where I had gone, I gave them an answer I had never given before: I’d been depressed, I said, and I needed the time off to get better.
Like so many others, the stigma of depression prevented me from telling people who needed to know that I was sick. I realize that now. Had I been willing to acknowledge my disease, I might have avoided those mistakes and maintained a decent relationship with my boss. By trying to hide my depression, I harmed my career and an institution that mattered a great deal to me.
So many stigmas have thankfully disappeared over the years. There used to be a stigma associated with having cancer, but that’s largely gone. Being gay used to be stigmatized, but in much of the country that’s not true anymore. In the 1960s, there was a stigma attached to being in the military; now service people are glorified in our culture.
It used to be that depressed people would be told they needed to shake it off, or “pull themselves up by their bootstraps.” That attitude has been fading as people come to understand that depression is an illness, and that those who have it can’t shake it off any more than someone with cancer can shake that disease off. As more of the estimated 16 million U.S. adults a year who suffer a major depressive episode tell their stories, the stigma will surely lift. Just not fast enough.
This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.