ETHAN HAWKE: All my heroes have one thing in common which is humility. And the ability to see yourself in the context of a larger community and see what you do as both important and unimportant. I believe that we are only as good as our time period. Like when you look at the great music of the late '60s and early '70s all those bands helped each other be great. They pushed each other up. If the artistic community is failing we all fail. I get inspired by other people's excellence. I don't want to be better than them.
I want everybody to be great, right? That's the healthiest idea. Oh, let me take a hero of mine when I was younger: River Phoenix, right. I was very jealous of River Phoenix. I've said that before in other places, but one of the things that was heroic to me about what he did – and people, so much has happened with the thought about this. But when I was – when River and I were 23, 22, the idea that you were like a young like teen star, right. You're on Teen Beat magazine, you're happening and agents want you to work in movies. The idea that you would go and play a gay character, a gay hustler was career suicide. But River never thought like that. The idea to think like that seemed small to him. Now it's kind of cool. Like with my kids and stuff, you know, with what's been happening – education about equality has been growing and growing, but when I was younger I mean that was before Kiss of the Spiderwoman. That was before, you know, there were a lot of revolutionary performances. But River's was really dangerous and incendiary.
And he was a real humanist about it. And I really admired that and when I get asked to play roles that might not suit my ego or might not suit my vanity I think of what River would say or how River would think. Tom Stoppard is a hero of mine, a living hero, a guy. I was in a rehearsal with him for nine months doing Coast of Utopia. This story of mid-nineteenth century Russian radicals. This is a man whose artistic flower is still blooming in his seventies. And why is it still blooming? Because it's a work ethic thing. He's never been about anything but the joy of creativity. And when he comes to rehearsal, at first you're intimidated and before you know it you're engaged because he's talking to you and asking you and provoking you. And he also wrote everybody who worked on the show - there was this huge cast like 100 people. He wrote everybody a personal thank you note for dedicating time out of their life to help his play come forward and he knows what a sacrifice was and how valuable their time is.
And he writes their name and he knows their name and he – and it's very – there's a humility to it. That humility is very inspiring to me. Robert Benton, director of Places in the Heart, who wrote Bonnie & Clyde along with a million other things, you know, when you meet these guys there's a great humility to them. I was doing this play Ivanov, right. This Chekhov play. It was so hard and I was killing myself with this character.
He commits suicide at the end of it. It's a very painful performance to give. And I was so nervous and opening night was coming, and I was getting so upset during the show that I was really hurting my voice. But I couldn't stop, and I was a nightmare to be with. And all of a sudden Hurricane Sandy happened and the theater shut down. And the lights didn't work and the New York Times wasn't going to cover the play. And all of a sudden you realize oh shit, you know. I mean there's so much that it's a luxury to be nervous. It's a luxury that this theater even exists to create this opportunity for me no less that anybody comes. After the hurricane nobody came. Man I was doing a play when September 11th happened. Nobody came to the play for a couple of weeks it seemed like. And so I feel, you know, Phil Hoffman used to say this all the time, that it's the most important thing in the world and it doesn't matter, and you have to hold both those – that coin together and flip it around. It's all true all the time.
- Ethan Hawke is inspired by others' excellence and ability to see the context of the larger community, those who value their work but don't take it too seriously.
- One of his heroes, River Phoenix, exhibited this kind of humility by taking on roles that were meaningful to him but were seen as controversial.
- "Phil Hoffman used to say this all the time, that it's the most important thing in the world and it doesn't matter, and you have to hold that coin together and flip it around. It's all true all the time," he says.
Indeh: A Story of the Apache Wars
- Ethan Hawke on Donald Trump, Racism, Political Correctness, and ... ›
- Ethan Hawke: Indeh, the Apache Wars, and human nature - Big Think ›
- A study provides further confirmation that a prolonged lack of sleep can result in early mortality.
- Surprisingly, the direct cause seems to be a buildup of Reactive Oxygen Species in the gut produced by sleeplessness.
- When the buildup is neutralized, a normal lifespan is restored.
We don't have to tell you what it feels like when you don't get enough sleep. A night or two of that can be miserable; long-term sleeplessness is out-and-out debilitating. Though we know from personal experience that we need sleep — our cognitive, metabolic, cardiovascular, and immune functioning depend on it — a lack of it does more than just make you feel like you want to die. It can actually kill you, according to study of rats published in 1989. But why?
A new study answers that question, and in an unexpected way. It appears that the sleeplessness/death connection has nothing to do with the brain or nervous system as many have assumed — it happens in your gut. Equally amazing, the study's authors were able to reverse the ill effects with antioxidants.
The study, from researchers at Harvard Medical School (HMS), is published in the journal Cell.
An unexpected culprit
The new research examines the mechanisms at play in sleep-deprived fruit flies and in mice — long-term sleep-deprivation experiments with humans are considered ethically iffy.
What the scientists found is that death from sleep deprivation is always preceded by a buildup of Reactive Oxygen Species (ROS) in the gut. These are not, as their name implies, living organisms. ROS are reactive molecules that are part of the immune system's response to invading microbes, and recent research suggests they're paradoxically key players in normal cell signal transduction and cell cycling as well. However, having an excess of ROS leads to oxidative stress, which is linked to "macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging." To prevent this, cellular defenses typically maintain a balance between ROS production and removal.
"We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation," says senior study author Dragana Rogulja, admitting, "We were surprised to find it was the gut that plays a key role in causing death." The accumulation occurred in both sleep-deprived fruit flies and mice.
"Even more surprising," Rogulja recalls, "we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies." Fruit flies given any of 11 antioxidant compounds — including melatonin, lipoic acid and NAD — that neutralize ROS buildups remained active and lived a normal length of time in spite of sleep deprivation. (The researchers note that these antioxidants did not extend the lifespans of non-sleep deprived control subjects.)
Image source: Tomasz Klejdysz/Shutterstock/Big Think
The experiments
The study's tests were managed by co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows at HMS.
You may wonder how you compel a fruit fly to sleep, or for that matter, how you keep one awake. The researchers ascertained that fruit flies doze off in response to being shaken, and thus were the control subjects induced to snooze in their individual, warmed tubes. Each subject occupied its own 29 °C (84F) tube.
For their sleepless cohort, fruit flies were genetically manipulated to express a heat-sensitive protein in specific neurons. These neurons are known to suppress sleep, and did so — the fruit flies' activity levels, or lack thereof, were tracked using infrared beams.
Starting at Day 10 of sleep deprivation, fruit flies began dying, with all of them dead by Day 20. Control flies lived up to 40 days.
The scientists sought out markers that would indicate cell damage in their sleepless subjects. They saw no difference in brain tissue and elsewhere between the well-rested and sleep-deprived fruit flies, with the exception of one fruit fly.
However, in the guts of sleep-deprived fruit flies was a massive accumulation of ROS, which peaked around Day 10. Says Vaccaro, "We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut." She adds, "I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research."
The experiments were repeated with mice who were gently kept awake for five days. Again, ROS built up over time in their small and large intestines but nowhere else.
As noted above, the administering of antioxidants alleviated the effect of the ROS buildup. In addition, flies that were modified to overproduce gut antioxidant enzymes were found to be immune to the damaging effects of sleep deprivation.
The research leaves some important questions unanswered. Says Kaplan Dor, "We still don't know why sleep loss causes ROS accumulation in the gut, and why this is lethal." He hypothesizes, "Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain. Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these."
The HMS researchers are now investigating the chemical pathways by which sleep-deprivation triggers the ROS buildup, and the means by which the ROS wreak cell havoc.
"We need to understand the biology of how sleep deprivation damages the body so that we can find ways to prevent this harm," says Rogulja.
Referring to the value of this study to humans, she notes,"So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it. We believe we've identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies."
