The science of addiction: a personal struggle to kick cocaine gives a neuroscientist unique insights
Having survived a decade of drink and drugs as a young woman, Professor Judith Grisel focused all her determination on writing a book about addiction
When Professor Judith Grisel sat down to write her book Never Enough (a guide to the neuroscience of addiction that has been her lifes work), she didnt expect to share so much of her own story. Nevertheless the resulting chapters are a collision of the personal and professional, detailing the deep links between her work life and the decade of drug and alcohol addiction that almost destroyed her.
On paper, Grisel was an unlikely candidate for going off the rails. One of three children, she describes a privileged upbringing in a progressive, suburban area of New Jersey. With an airline pilot father and a mother who was a registered nurse, Grisel remembers growing up in a perfect-looking family.
As her research would go on to help demonstrate, there was no single factor that predicted her drug problems. Neuroscientists have found a complex blend of nature and nurture at work in addictive tendencies and their research shows that many genetic, epigenetic and environmental factors work together in complex ways that often remain elusive.
Why me? is the question that underpins much of Grisels research, and she continues to wonder why friends who drank heavily with her in high school were spared addiction. In Never Enough she offers a smorgasbord of theories behind her own and others predisposition to addiction: an extreme personality and love of risk-taking, trying drugs at a young age, lower levels of endorphins in the brain, potential hypersensitivity to the neurological rewards of drugs alongside, more surprisingly, her own parents strict response to her behaviour.
If they had just been a little more lax, if I hadnt been the first child, I probably could have been normal, she reflects. Grisel did not experience the childhood poverty, insecure housing or abuse we have come (rightly) to associate with some drug users histories. Instead she believes the misery within her parents relationship and the pressure she felt to keep up appearances had the greatest impact on her trajectory. Their marriage was so dysfunctional that my mother eventually got an annulment from the Pope but we never acknowledged it at the time. As a kid I felt like a prop in this play of the perfect family.
A pivotal moment came when, aged nine or 10, Grisel found her mother crying at the kitchen sink. I asked her what the matter was and she answered that she was crying because she was so happy. My stomach sank a thousand feet because I knew it wasnt true but I also knew there was no way to reach the truth. Her mothers insistence that the family ignored the reality of their problems and instead went along with a pretence of happiness had a profound and negative impact on the way Grisel herself came to understand her own emotions and place in the world.
What I learned to do in that moment, she explains, was to doubt my reality; to realise that what was critical in life was the story, the veneer. And that felt like dying.
So began Grisels search for a way to escape her everyday life, a life that felt false and full of pressure to go along with the pretence, and instead to find a way to feel something that felt like the truth. It started with an obsession with reading books, I would read constantly, upside down if I had to, and then aged 13 (reaching a key developmental point when the teenage brain is primed for risky behaviour) she had her first drink. I thought, this is how people get through life. I can pretend all this stuff, because I can have this little secret where Im nice and warm inside, remembers Grisel. It was the first time in my life I remember feeling relaxed.
Grisel swiftly progressed to the solace of daily drinking, smoking marijuana and regular drug use. I loved being able to connect to my true self and I only seemed to be able to do that when I was wasted, she explains. Unsurprisingly, she was soon in trouble at home and school, trouble that escalated through her teenage years until she was kicked out by her parents when she was 19 dropping out of her first year of college at the same time. After years of trying a range of ways to stop Grisel taking drugs her family now withdrew financial support entirely. As she left home, despite her brawny high school football player brother crying in the street, she felt exhilarated: I felt like all the restraints were off and things got very bad after that.
Increasingly detached from her parents, who she barely saw over the next four years, Grisels life became entirely focused on drugs. I was scraping by on nothing but lies and evasion and my only priority was staying loaded. Now injecting cocaine, her dedication to the next hit led to frequent homelessness and unemployment. When she did find work she stole from the till, she regularly took credit cards from strangers and ruthlessly stole money and drugs from friends. Soon she was facing lunatic dealers and DEA agents with a single-minded determination that she also credits with her subsequent scientific tenacity.
The depravity of Grisels addicted life, described in the memoir chapters of Never Enough, illustrates the vicious cycle of the A and B process she explains in the scientific sections of her book. When humans engage in any mind-altering activity, the effects are known as the A process. Whether its the sedation of alcohol or the rush of cocaine, users often feel pleasure from the initial use of their drug of choice. But as Grisel is at pains to explain, There is no free lunch.
She believes people might make better choices if normal brain function was more widely appreciated. The brain adapts to any addictive substance or activity by producing the exact opposite effect, says Grisel. This opposite state, known as the B process, is led by the brains drive to return to its baseline state and its why hangovers and comedowns are such unpleasant experiences. Our brains are so efficient at returning to normal that with regular use we need more and more of the drug or activity to feel the A process and the oppositional B process kicks in almost instantaneously. Soon, as Grisel herself experienced, we need the drug just to feel normal and without it we only feel the negative impact of the B process.
With addiction rates rising steeply, helping people avoid being imprisoned in this cycle is a priority for many worried parents, case-workers, researchers and Grisel herself. But, just as a simple set of causes of addiction doesnt seem to exist, there doesnt appear to be a magic recipe for recovery either. Grisel describes her own transformation from addict to sober scientist as a collection of coincidences and luck. I was inexplicably fortunate. I think I was carried through by circumstance, she says.
A lucky break led to better housing and a move away from injecting cocaine. After a terrifying encounter with her reflection in the mirror, the final push she needed to start her recovery came from her parents. In a crucial moment of compassion from her father, he told her he wished only happiness for her life and the 23-year-old finally realised just how unhappy she was.
A drug-treatment facility in Minnesota was followed by a three-month stay in a womens halfway house and then Grisel began to repair her life. A key motivation for staying sober was her determination to find a cure for addiction. At the beginning of her career, Grisel and others in her field were convinced they would swiftly find that cure, but as neuroscientific understanding has deepened it has revealed just how much we dont understand. In the book, Grisel reflects, I was shocked that I couldnt say that neuroscience is making great strides. It didnt seem true to me.
Though she cant yet offer a magic switch to turn off addiction, She now believes much of the answer lies not in manipulating DNA but in encouraging human love, compassion and connection. With more high-potency drugs available more widely than ever before, alongside a sea of addictive technology enticing adults and children to fritter away our lives checking updates just like users fritter away their lives snorting cocaine, Grisel believes we need a range of tactics to tackle the global problem of addiction. The people right next to us are an obvious place to start, she adds. Human relationships and connections are the low-hanging fruit.
With her own 16-year-old daughter and grown-up stepsons she and her husband have prioritised staying emotionally connected to their children and, when they are worried about behaviour, sharing their own feelings rather than telling their children what to do. I will say, I love you and Im really concerned about this. If you need help, I will give it to you, Grisel says. But I will also be clear that I am not going to enable the behaviour. Despite choosing to parent differently from the way that she was brought up, Grisel now reflects on her parents with compassion, believing that if you have a child who is an addict, Its an almost impossible situation to be in and very hard to know what to do.
Decades of research and experience have led Judith Grisel to believe that the dominance of addictive substances and activities in contemporary life are leading society to the brink of an addictive black hole and that it is only by connecting with each other that we can avoid being sucked in. Right now were in a rising phase of escapism and pharmacology this epidemic of addiction is really an epidemic of avoidance. Above all we need better ways to cope with life and to be present to our experiences. Despite her concerns, she does have hope. Ultimately you cant avoid yourself. It didnt matter how high I got, I was stuck with myself. I think were soon going to get to that point as a society and then we might finally have our moment of truth. Then, Grisel believes, well discover that the way out of addiction was actually inside us all along.
Never Enough: the Neuroscience and Experience of Addiction by Judith Grisel is published by Scribe, priced 9.99. Buy it for 8.79 at guardianbookshop.comRead More
Should you wear white or black during the summer? Or that other burning fashion question: Is it OK to wear white after Labor Day? Oh wait, that question really isn't important. Let's get back to the summer question.
There are two answers to the black vs. white clothing question.
1. Wear White. A white object is white because it reflects white light, and white light is a combination of all the visible colors. This means that a white shirt (or pants) will reflect most of the light and not get hot. Simple, right?
2. Wear Black. But wait! What about the bedouin in the desert regions of North Africa? They often wear black clothing, and it's super hot there. It seems they wouldn't wear black unless there was an advantage. Maybe the black clothing prevents body heat from reflecting back on the human—thus keeping the body cooler than a white outfit.
OK. Let's be clear. This black vs. white clothing isn't exactly a settled issue. People actually study this stuff—here is an article from Nature published in 1980: "Why do Bedouins wear black robes in hot deserts?". There are clearly several situations to consider with the Bedouin clothing. But what about more common outfits, like a T-shirt? Should you wear a black or white T-shirt on a warm summer day?
The first thing to consider: Does a black shirt get hotter than a white one? I can explore this question with an infrared camera. You see, everything gives off light (electromagnetic radiation). Some super-hot things (like a lightbulb filament or a stove burner) are hot enough that this emitted EM radiation is in the visible spectrum, and we can see it. For most other objects, the emitted light has a wavelength that puts it outside the visible range. Most of this light falls in the infrared region.
Using a special camera, a sensor detects the infrared radiation and uses this to determine the object's temperature (for the most part).
So let's do it. Here are some shirts hanging out in the sunlight.
Now for an infrared image. Note: this is a false-color image. Since we can't actually see infrared light, different colors in this image correspond to different wavelengths in the IR region.
From this image I can get the temperature of the shirts. OK, technically there is a small problem measuring the temperature, but I will address that shortly. The black T-shirt on the right measured 131.0 Fahrenheit and the white one on the left was 111.8. Yes, it's clear the black shirt was hotter. Other than that, there were no real surprises.
But come on. You already knew this. In fact, you can even do your own experiment. Grab some paper—a white piece and a black piece. Place them outside in the same sunlight. You only have to wait a few minutes before picking them up to realize that the black paper is hotter.
Now for the second question. Does a white T-shirt reflect thermal radiation from your body back to your body to warm you up? The answer is yes. Perhaps the question should be: Does white reflect MORE thermal radiation than black clothing (I'm equating thermal radiation and infrared light—same thing). Is a white shirt "infrared white"? Does it reflect more infrared radiation than a black shirt?
How about another test. To measure the infrared reflectivity (not a real term) of different shirts, I set up the following experiment. There is a hot (but not too hot) iron that you can use to make your clothes wrinkle-free. This is my infrared source. I placed it around a corner so my infrared camera couldn't see it. Then I put different objects in front of the camera to see how they reflected this infrared light.
Let's start with something fun. Here is a tile board. It's the same stuff those whiteboards in classrooms are made of. What happens when infrared light hits it? This happens.
This is a composite image (in case you couldn't tell). The infrared camera I am using (the FLIR One) has both a visible light camera along with an IR camera. I cut out a part of the visible image and placed it on the IR image to make it more obvious what you are looking at. The important part is the bright spot in the middle of the board. That is a reflection from the iron. Oh, you want to see the iron too? Here you go.
Notice the reflection on the floor? That's because my smooth kitchen floor reflects infrared light, and you can see an image with the camera. Yes, that's awesome.
What about a white T-shirt?
No spot. It doesn't reflect much infrared. What about a black shirt? It pretty much looks the same in infrared.
So, although the two T-shirts look different to human eyes (in the visible light range), they are pretty much the same in infrared. That pretty much answers the second question about clothing. Does white reflect back more infrared radiation on your body? Nope. Just because it's white doesn't make it "infrared reflective."
Do you know what is very infrared reflective? Space blankets—those shiny mylar blankets that you can use in an emergency. You know what else makes a difference? Water. Here, check this out. This is an image of a T-shirt with some water on it next to a piece of mylar.
That darker stuff on the shirt is just a tiny bit of water. As the water makes a phase transition from a liquid to a gas, it takes energy. This energy comes from the rest of the liquid water, causing a drop in temperature. This is exactly why humans sweat—we cool off through the evaporation process. Also, check out the mylar on the right. It looks different because it's reflecting both the visible light and the infrared radiation. That makes it rather difficult to measure the temperature with an infrared camera, because you are seeing reflected light rather than emitted light.
Now is the time to discuss this emission vs. reflection problem. In the world of infrared cameras, different materials can have a different emissivity. The emissivity of an object can have a value between 0 and 1. If an object is only radiating infrared light and not reflecting it at all, that would be an emissivity of 1. Something that only reflects infrared light would have an emissivity of zero.
The T-shirts (both the black and the white) have an emissivity very close to 1—they don't really reflect much infrared radiation. But the mylar has an emissivity close to zero.
That pretty much answers the question. In most cases white clothes look just like black clothes in the infrared spectrum. They both reflect about the same amount of thermal radiation. That means you are going to be better off with white clothes, since they don't absorb as much visible light. But wait! Could there be a special case in which black is better?
Let's get back to the bedouin black clothing. What is going on here? Well, there is more to heating and cooling than just the color of the clothes. What about evaporation? What about wind? One possible reason for the black clothes is a type of chimney effect. The idea is that the black clothes heat up the space between the cloth and the human to promote an upward air current (like a chimney). This air current adds to the cooling of the human. But maybe you see the problem. You have to have an air space between the fabric and the skin. I don't know about you, but my shirts aren't that loose. I suspect that there are only a few people that wear clothes in the bedouin fashion—but for those people, you might want to stick to black.
But wait! There's more! There are so many variables in this black vs. white clothing question that this could be a great starting point for a science-fair experiment (you know … for kids). I'll be honest, I'm not too keen on science fairs in general, but if you are going to do a project, this seems like a great thing to study. Here are some ideas to get you started.
- Data collection: If you want to get an infrared camera (they are very useful), you can collect some great data. If you don't have an IR camera, you could still collect meaningful data using some small temperature sensors.
- Do different types of clothing material reflect infrared light differently? What about those "breathable" shirts? What about other stuff, like silk?
- Get a bunch of people and measure their body temperatures with loose vs. tight clothing.
- What about the wind? Does the color of clothing matter if there is a slight breeze?
- What about the humidity in the air? What impact does it have on clothes of different colors?
So you have $52 million burning a hole in your pocket and just can’t decide what to do with it. Buy a private island? Too cliché. A new McLaren? You have enough of those. Pay off college administrators? Your kids have already graduated. But have you considered a stay at the International Space Station, the world’s premiere space hotel?
This is the proposal put forth last week by billionaire hotelier Robert Bigelow, whose company, Bigelow Space Operations, says it will send up to 16 private astronauts to the ISS in the coming years. Bigelow says $52 million will buy you a seat on a SpaceX rocket and a one- to two-month stay in orbit. This depends, of course, on SpaceX getting its commercial crew operations off the ground, which it expects to do by 2020. There aren’t many further details about Bigelow’s plans, but since 2018 he’s put down “substantial sums” to reserve four future SpaceX flights specifically for orbital tourism. (Bigelow has also promised space hotels by 2021, a timeline that is optimistic at best.)
A trip to space is definitely a luxury, but life in orbit? Anything but. In fact, when NASA astronaut Peggy Whitson, who has spent more time in space than any other American, returned from her last trip to the ISS and was asked to describe her experience, she said, “I would call it a camping trip.” Camping … in space? If that sounds like a good time, here’s what the ultra-rich can expect during their stay at the space station.
The ISS is the largest object ever put into space, but by terrestrial standards it’s still pretty cramped. The station has a pressurized volume of only 32,333 cubic feet, which is about the same as a Boeing 747. But only a third of that is habitable. Unlike a private jet, this space will be shared 24/7 by up to 10 people—six government astronauts and four private astronauts. Sounds like a recipe for cabin fever, but if Scott Kelly could spend a full year on the station, what’s one or two months?
Sleeping accommodations on the ISS are cozy. Each astronaut gets their own sleeping pod, which is just big enough to fit a person and a laptop mounted on the opposite wall. Tourists on the ISS don’t need to worry about bringing a pillow or blanket, either. Pillows are superfluous in space, and their blanket will be a sleeping bag strapped to the wall. Sweet dreams!
The ISS has a kitchen, but if tourists are expecting farm-to-table fare they’ll be very disappointed. An astronaut’s diet involves a lot of rehydrated power foods, but comfort foods like brownies and peanut butter and jelly sandwiches are also available. Hopefully the tourists like tortillas, because there will be a lot of them.
Nothing goes better with endless burritos than a little tequila, but the ISS is drier than an AA meeting. NASA tried to get some booze into orbit back in the ’70s, but the negative public reaction over sending sherry to the Skylab space station quickly killed the plan.
As for the bathroom situation, well, its slightly better than digging a latrine on a camping trip, but not by much. To urinate, astronauts pee into a vacuum funnel in a high-tech porta potty. Defecating is pretty much the same, but more perilous. Astronauts need to make sure their excrement hits a roughly dish-sized hole, which suctions it into a plastic bag. This is a good incentive for ISS tourists to make sure they’re eating enough fiber, because if the toilet gets backed up or too full, well, let’s just put it this way: In space, everything floats, and someone’s got to wrangle it.
The ISS isn’t just a poop rodeo, however. During a tourist’s month in space, there will be plenty of time for leisure. They’ll be able to drift around the cupola, taking in a view of Earth that only a few hundred people in history have ever enjoyed. They’ll be able to float through the station catching M&Ms in zero g, pump some iron in the ISS gym, or maybe make a few funny videos to send home to friends. Data will cost $50 per gigabyte, but if you’ve already paid $52 million to get there, what’s a few grand more to tweet from orbit?
This is all a good way to spend a day or two, but how to spend the rest of the month? The astronauts surely have some good stories, but they won’t be around to shoot the breeze. NASA plans their days down to the minute, and most of the time they’ll be doing science experiments or station maintenance. How about a spacewalk? This is, at best, unlikely. The suits used for extravehicular activities are basically personal spacecraft and cost over $10 million each. Aside from that, hanging out in the vacuum of space is dangerous business. Astronauts have nearly drowned and run out of oxygen in their suits, so it’s probably best left to those who have spent their whole careers training for it.
If that still sounds like a good way to spend a month, Bigelow is taking reservations. It’d probably be a good idea to inquire about the refund policy, however. When space tourism on the ISS was first getting started in the early 2000s, only seven tourists managed to catch a ride on a Russian Soyuz rocket before the tourist program was put on hiatus. One would-be Japanese astronaut sued the space tourism company Space Adventures to recoup a $21 million down payment on a flight that never happened due to medical reasons. More recently, nearly 300 people lost the majority of their $100,000 down payment to fly to space with Xcor Aerospace when the company went bankrupt. Caveat emptor!
Richard Godwin catches up with five pensioners, aged up to 108, who thrive on extreme exercise
Edwina Brocklesby: triathlete, 76, Kingston-upon-Thames
I didnt do any exercise at all until I was 50. I remember trying out for the long-jump team at university for a laugh and I couldnt move for two weeks afterwards. So that was the end of my athletics career. And then I had three children and I was busy with my job. I was a social worker and ran two adoption agencies.
One day, I went to see an old friend from Nottingham University who was running a marathon. I thought that would be fun to do, at least a half marathon, anyway. I came back and told my husband and he laughed and said I wouldnt even be able to run as far as Northampton, which was about three miles from where we lived at the time. Its good to have a challenge like that! Sure enough, it did inspire me to run my first half marathon.
Then my husband died when I was 52. By then I had a small group of running friends and they were brilliantly supportive. I trained as a counsellor myself, but I found running better than counselling for dealing with grief. For one, you always feel better after youve been for a run as the endorphins kick in. But I think what is more important is the social element. Youre with people who support you and value you. You can talk if you want to, or you can be silent if you want to.
The running club was only small, but it did have one place in the London Marathon and thats when it became more serious for me. I ran my first marathon in 1996, when I was 53. I moved to London and became a member of the Serpentine Running Club and, with them, I completed my first London Triathlon when I was 58. I dont have an anterior cruciate ligament in either knee my daughter told me that Id need surgery if I kept pounding the streets like I used to and thats how I got into cycling and swimming as theyre a little easier on the joints. When I started swimming, at 56, I couldnt do crawl at all and swam breaststroke with my head above water like most women of my age. But swimming is a wonderful feeling. It might have something to do with our spending the first nine months of our gestation suspended in water.
Theres so much evidence that if you keep physically active, you dont experience some of the difficulties associated with ageing. There are lower rates of type 2 diabetes among the active, but falling over is the biggest thing. If you can keep your bone and muscle strength up, youre less likely to fall and you might also be able to prevent yourself from hitting the ground if you do fall. Falls are one of the things that costs the NHS the most money.
Im getting slower as I get older, of course I am. I do manage to run 5k, but I walk a bit more. I feel lucky that I can still jog along the Thames.
Edwina Brocklesby is the director of Silverfit, a charity that promotes physical activity among ageing people. She is also the UKs oldest Ironman triathlete. She was recently awarded the British Empire Medal
Eddy Diget: personal trainer, 74, Milton KeynesRead More
The large outer leaves of the vegetables were “literally riddled with holes, more than half their substance being eaten away.” With each step he took around the ravaged cabbages, tiny swarms of little ash-gray moths rose from the ground and flitted away. This was, it appears, the first record in the United States of the diamondback moth, an invasive pest that in its larval form shows a fondness for cruciferous vegetables. By the late 1800s the moths were chewing through the leaves of cabbages, brussels sprouts, collards, and kale from Florida to Colorado.
To fight this invasion, farmers started bombarding their fields with primitive pesticides. This worked. Or seemed to. It killed most of the moths, but those that survived the poison reproduced, and the population bounced back stronger than ever. For decades, one pesticide after another failed as the moths evolved to withstand it. Even the grievously toxic DDT was no match for the diamondback. Beginning in the late 1950s, agriculture experts started to abandon the idea of eradication and adopted a new strategy. Farmers would leave the moths alone until their numbers exceeded a certain threshold, and only then would they deploy pesticides. Remarkably, this helped. The moths did not die out, but the pest could be managed and crop damage held in check.
When Robert Gatenby heard this history of the diamondback moth in 2008, he immediately latched onto it. Gatenby is not a farmer nor an agronomist nor a fan of cruciferous vegetables—in fact, he deeply loathes brussels sprouts. He is a radiologist by training and heads the radiology department at the H. Lee Moffitt Cancer Center in Tampa, Florida. But unlike your typical doctor, he is also obsessed with the evolutionary principles put forth more than 150 years ago by Charles Darwin. The story of the diamondback moth appealed to Gatenby as a useful metaphor for his own project—one concerned not with crops but with cancer.
Like the diamondback moth, cancer cells develop resistance to the powerful chemicals deployed to destroy them. Even if cancer therapies kill most of the cells they target, a small subset can survive, largely thanks to genetic changes that render them resistant. In advanced-stage cancer, it’s generally a matter of when, not if, the pugnacious surviving cells will become an unstoppable force. Gatenby thought this deadly outcome might be prevented. His idea was to expose a tumor to medication intermittently, rather than in a constant assault, thereby reducing the pressure on its cells to evolve resistance.
Just as ecologists allow for a manageable population of diamondback moths to exist, Gatenby’s method would permit cancer to remain in the body as long as it doesn’t spread further. To test this idea, Gatenby got permission in 2014 to run a trial on advanced-stage prostate cancer patients at Moffitt. The patients had cancer that no longer responded to treatment; their drug-resistant cells were winning an evolutionary battle within the body, surviving an onslaught of toxic drugs where weaker cancerous cells had succumbed. The hope was that, by using a precise drug-dosing scheme developed using evolutionary principles, they could slow the rise of the mutations that would endow some cancer cells with the fitness to survive. Gatenby's name for the approach was adaptive therapy.
One of the patients in the trial was Robert Butler, a British oil-exploration engineer who had retired in Tampa. In 2007 he was diagnosed with prostate cancer, and seven years later, after taking the drug Lupron and getting blasts of radiation, his prostate tumor had progressed to stage 4, advanced cancer. Butler did not give up, though. He tried a newly approved immunotherapy treatment—one that involved having cells from his blood sent by courier to a facility outside Atlanta, where they were mixed with a molecule that activates immune cells, and then shipped back to Florida to be injected back into him. The treatment was expensive—its sticker price can be as high as $120,000—but the threat that the cancer would progress remained.
When Butler and his wife showed up at his oncologist’s office at the Moffitt Cancer Center in August 2014, they braced for what would come next; they had heard about invasive treatments, like radioactive seed implants. So they were intrigued when the doctor told them about Gatenby’s trial and asked if Butler wanted to participate. He would take a powerful and exceedingly expensive drug called Zytiga, but not in the scorched-earth, kill-all-the-cells fashion that is standard. Instead he would receive only as much Zytiga as was necessary to stop the cancer from growing. The idea was radical and counterintuitive. His last best shot at escaping death from his cancer was to give up on curing it.
Knowing the modified Zytiga regimen wasn’t designed to rid him of cancer left Butler, the engineer, with a question about how the doctors would measure the success of their new treatment approach. He asked, “How do we know this stuff is working?” And one of his doctors replied, “Well, you won’t be dead.”
In the United States we use military metaphors when we talk about cancer. We battle and we fight, and if we survive, we’re victorious. The attitude traces back in part to 1969, when the Citizens Committee for the Conquest of Cancer ran an ad in The Washington Post and The New York Times imploring the president with the words “Mr. Nixon: You can cure cancer.” The call to action helped trigger the country’s “war on cancer” with a determination that, using enough medical weaponry, the malignant foe could be obliterated.
By the mid-1970s, however, signs were beginning to emerge that certain strategies aimed at total eradication were liable to backfire. Against this backdrop, a cancer researcher named Peter Nowell published a seminal paper in Science in 1976. Nowell conjectured that evolutionary forces drive certain cell populations in tumors to become progressively more malignant over time. The cells inside a tumor are in competition, not only with nearby healthy cells, Nowell argued, but also with each other. Nowell suggested—and later research confirmed—that certain DNA alterations grant cancer cells resistance against chemotherapy or other treatments, causing them to edge out drug-sensitive cells through a process of natural selection.
Nowell conveyed his ideas to his students at the University of Pennsylvania School of Medicine, sometimes smoking a cigarette as he lectured. His theories were respected but slow to catch on. He emphasized that tumors may become deadlier as they accumulate more genetic errors. It was an idea ahead of its time. Scientists back then didn’t have the technical capability to measure all the changes in the vast genomes of tumor cells. Instead, they could sequence only little tidbits of DNA at a time, and most scientists viewed cancers as the fruit of just a few genetic mutations.
One of the medical students listening to Nowell lecture in the late 1970s happened to be a young Bob Gatenby. But Nowell’s ideas didn’t make a strong impression on him, Gatenby says; instead, what inspired him was what he witnessed in his first years as a practicing radiologist on the bloody front lines of the war on cancer.
By the mid-1980s, Gatenby had secured a job at the Fox Chase Cancer Center in Philadelphia. At that hospital and others around the country, clinical trials were putting breast cancer patients through an extreme treatment: a combination of a potentially lethal dose of chemotherapy followed by a bone marrow transplant. The treatment was harrowing. The women had diarrhea and nausea, and some had so much lung damage they had difficulty breathing. Others experienced liver damage and weakened immune systems that left them vulnerable to serious infections. As a radiologist, Gatenby’s job was to interpret x-rays and other scans of the patients, and he saw the treatment failing. Out of more than 30,000 women with breast cancer in the US who underwent the procedure between 1985 and 1998, as many as 15 percent died from the treatment itself. “What happened was these women suffered horribly, and they weren’t cured,” Gatenby says.
Around the same time as the breast cancer trials, the father of a colleague of Gatenby’s came to the hospital to receive an initial, aggressive round of chemotherapy for lung cancer. According to the colleague, her father arrived on a Friday with no apparent symptoms and was dead by Monday. “That event to me was very traumatizing,” Gatenby recalls, and the cause to him seemed obvious. “I couldn’t understand why you would treat someone with a fatal disease and kill them with your therapy. It just didn’t feel right to me.” During this fraught period, Gatenby’s own father died from esophageal cancer.
Gatenby felt there must be a better way to treat cancer—to outsmart it rather than carpet-bomb it. He had studied physics in college and believed that biologists could leverage equations to capture the forces driving cancer the same way physicists use math to describe phenomena like gravity. Whereas Nowell had put forth general theories about how cancers followed evolutionary principles, Gatenby was taking a further leap: He wanted to figure out a way to describe the evolution of cancers with mathematical formulas.
By 1989, Bob Gatenby was preoccupied with modeling the evolution of cancers. During the day he would scrutinize the x-rays of cancer patients, and at night, after he and his wife had put their young kids to bed, he would sit at the kitchen table in their suburban Philadelphia home and pore over medical journals. The patterns he started seeing in the literature led him to a question: What if cancer cells outcompete normal, healthy cells in the body in the same way an animal species edges out its competitors in nature?
Gatenby recalled that ecologists had come up with equations to describe the balance between predators and prey. As an undergraduate at Princeton University, he had learned the classic example of the math that plotted how growing populations of snowshoe hares fuel the rise of the lynx that feed on them. He began dusting off old books and buying new ones to educate himself on species interactions.
For a year Gatenby read and mulled. Then, in 1990, on a family trip to the Atlantic coast of Georgia, he found himself stuck in a hotel room one afternoon with his two napping children. Out of nowhere, an idea presented itself. He grabbed a pad of hotel stationery and a pen and began scribbling down some key formulas from population ecology. Those formulas, called Lotka-Volterra equations, have been used since the 1920s to model predator-prey interactions and, later, competition dynamics between species, and were among the ones he had recently brushed up on at home. Gatenby thought this set of formulas could also describe how tumor cells compete with healthy cells for energy resources such as the glucose that fuels them.
When he returned to Philadelphia, he spent what time he could at a typewriter composing a paper that laid out this theoretical model. As soon as he finished, he showed it to some colleagues. He didn’t get the response he had hoped for: They thought it was ridiculous to try to use ecological equations to model cancer. “To say that they hated it would not do justice to how negative they were about it,” he says. His peers thought that a brief set of formulas couldn’t capture cancer’s seemingly infinite complexities.
Louis Weiner, who worked alongside Gatenby at the time, recalls that their colleagues viewed Gatenby’s ideas as offbeat. “Treatment orthodoxy at that time favored high-intensity, dose-dense treatments aiming to eradicate every last tumor cell in a cancer patient,” says Weiner, who is now director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. “Bob’s perspective was antithetical to those beliefs.”
But Gatenby pressed on and succeeded in getting the paper, chock-full of Lotka-Volterra equations, accepted in the prominent journal Cancer Research in 1991.
Despite the publication of his theory, he still couldn’t convince oncologists that his idea had practical merit. “I think that they felt intimidated,” Gatenby says. “Most physicians are mathematically illiterate.” He found that the medical establishment was reluctant to publish much of his follow-up work.
In the years afterward, Gatenby moved up the ladder to lead the department of diagnostic imaging at Fox Chase Cancer Center. He was later appointed head of the department of radiology at the University of Arizona College of Medicine in Tucson, and he continued to garner recognition for his skilled interpretation of scans and to receive federal grants to study cancer.
Then, in 2007, the Moffitt Cancer Center offered Gatenby a job as chair of the radiology department. He had a condition: He would come if the hospital created a division where he could pursue in earnest the link between Darwin’s principles and cancer. The Integrated Mathematical Oncology Department, born from this negotiation, is the first math department in a cancer hospital, he says. Finally, Gatenby had a place where he could put his ideas to the test.
Gatenby arrives at his corner office at Moffitt most days by 7 am. He’s 67 now, and his hair is gray at the temples, but his eyebrows are still brown. His children—the ones who were napping in that hotel room when he jotted down his Darwinian inspiration—now have children of their own, and he has the “I ♥ Grandpa” coffee mug to prove it. A hospital lanyard around his neck, he rolls up his crisp shirtsleeves and settles down at his desk. Outside his office, roughly 30 scientists and PhD students spend their days researching patterns of cancer growth using equations like those describing population dynamics.
To Gatenby's knowledge, no one had endeavored to exploit evolution against cancer in a clinical trial until he developed his prostate cancer experiment. He picked prostate cancer to test this approach partly because, unlike other cancers, a routine blood draw for a molecule called prostate-specific antigen (PSA) can offer an immediate proxy for the cancer’s progression.
To design a clinical trial, Gatenby and his Moffitt collaborators first needed to account for their idea that tumor cells vie against each other for resources. They turned to game theory to plot this dynamic and plugged the numbers into the Lotka-Volterra equations. The computer simulations they ran with these equations estimated how quickly drug-resistant cells would outcompete other tumor cells when exposed to the continuous dosage of Zytiga typically given to advanced-stage prostate cancer patients.
In the simulations, the typical administration of the drug led to drug-resistant cancer cells rapidly running rampant. The treatment would ultimately fail each time. That bleak outcome matched up with the results seen in hospital records. In contrast, the computer simulations suggested that if Zytiga were administered only when the tumor seemed to be growing, then the drug-resistant cells would take much longer to gain enough advantage to overrun the cancer.
In 2014 the Moffitt team managed to get the first small study to test this adaptive therapy approach off the ground, recruiting Robert Butler and a small group of other men with advanced prostate cancer. Butler’s oncologist explained to him how it would work. He would remain on the Lupron he’d taken for years, and each month he would go to the hospital to get his PSA level tested, to judge whether his prostate tumor was growing. Every three months, he would get a CT scan and a full-body bone scan to watch for disease spread. Whenever his PSA level edged above where it stood when he entered the trial, he would start taking the more powerful Zytiga. But when his PSA level fell to under half of the baseline, he could go without Zytiga. This is appealing because Zytiga and drugs like it can cause side effects like hot flashes, muscle pain, and hypertension.
The Moffitt approach also promised to be far cheaper than taking Zytiga continuously. When purchased wholesale, a one-month supply costs almost $11,000. Butler had health insurance, but even so, his first month’s supply each year would set him back $2,700 in out-of-pocket copayments, and $400 a month thereafter. Going off the drug whenever his PSA level was low would translate to huge cost savings.
Butler was participating in a so-called pilot trial, which was less rigorous than a large clinical trial, because it didn’t randomly assign patients to receive the experimental or standard treatments. Rather, the study relied on a group of patients treated outside the trial as well as results from a 2013 paper on Zytiga to come up with a benchmark for how patients typically fare when receiving continuous dosing of the drug.
When the early results of their new trial trickled in, the Moffitt scientists were gratified and relieved. Ahead of the trial, “we were, to be honest, terrified,” Gatenby says. The benefit of adaptive therapy appeared to be huge. Of the 11 men in the study, one left the trial after his disease spread, but most were living longer than expected without their cancer progressing. Men getting continuous dosing of Zytiga go a median of 16.5 months before the cancer becomes resistant to the drug and spreads. In comparison, the median time to progression for the men receiving adaptive therapy was at least 27 months. Moreover, they were on average using less than half of the standard amount of Zytiga. Joel Brown, an evolutionary ecologist and one of Gatenby's collaborators, said the team felt a moral obligation to get the word out: “The effect was so big that it would be unethical not to report it immediately,” he says.
They published a report in 2017, far earlier than anticipated, to a generally positive reaction from prostate experts—particularly because it suggested a way that people with cancer might live longer with less medication. “If you can reduce side effects, I think that’s fantastic,” says Peter Nelson, an oncologist who studies prostate cancer at the Fred Hutchinson Cancer Research Center in Seattle. “Conceptually it’s a beautifully simple approach.” Jason Somarelli, a biologist at the Duke Cancer Institute, calls Gatenby a pioneer: “He’s turning cancer into a chronic disease.”
Butler, who is 75, has gone for long periods off Zytiga—with stretches lasting as long as five months. “I’m now the poster boy, they say,” Butler says. He’s one of the best responders in the study.
Some doctors are already trying adaptive therapy on patients outside of clinical trials. In 2017 a doctor in Oregon, inspired by Gatenby’s pilot study, started a prostate cancer patient on a modified version of the approach when he refused the standard continuous dosing. She has since started treating a second man using adaptive therapy. Other oncologists might be doing the same. It’s nearly impossible to know for sure, because adaptive therapy doesn’t require government approval. The protocol uses already-approved medications, and the US Food and Drug Administration doesn’t police specific dosing schedules.
Experts urge caution, however. The prostate cancer study was very small, and without a randomly assigned control group the results aren’t truly reliable. While the majority of the men in the trial remain stable, four more saw their cancer progress since the paper came out. “This is an approach that now needs to be carefully studied in prospective clinical trials before it is adopted into clinical practice,” says Richard L. Schilsky, chief medical officer for the American Society of Clinical Oncology. Years could pass before a large-scale test of adaptive therapy takes place. Len Lichtenfeld, interim chief medical officer of the American Cancer Society, echoes Schilsky’s concerns. “Is it intriguing? Yes,” Lichtenfeld says. “But there is still a long way to go.”
Gatenby agrees that adaptive therapy needs rigorous testing. He conveys a kind of humility you don’t see very often in the upper reaches of medical science. He told me multiple times that he is not an interesting subject to write about, and more than once I heard close colleagues mangle the pronunciation of his name (which is pronounced GATE-en-bee); apparently he had never corrected them. But when he believes in something, he doesn’t relent. And he believes in adaptive therapy. “He’s like a teddy bear, but underneath that soft exterior he’s made of steel,” says Athena Aktipis, who studies theoretical and cancer biology at Arizona State University and has collaborated with Gatenby.
Late last year, Gatenby presented his work at a meeting of prostate cancer specialists. In the question and answer session afterward, an attendee shared his surprise at the results. “I guess what you’re saying is that we’ve been doing it wrong all these years,” the man mused, according to Gatenby. “I was literally speechless for a few moments,” Gatenby admits, “and then I said, ‘Well, yeah, I guess that’s what I’m saying.’” He is still dwelling on the exchange and wishes he could somehow find the man and apologize. He’s not taking back what he said; he does think the profession can do better. But, he says, “I should have been more diplomatic.”
In 2016, a couple dozen researchers gathered in a conference room at an ultramodern genetic sequencing center along the banks of the River Cam, 9 miles outside of Cambridge, England. The gathering brought together experts to discuss how principles of ecology might apply to cancer. When they took a break, their idea of fun was to play a round of “Game of Clones,” in which a small group of scientists pretended to be cancer cells trying to persuade the maximal number of other researchers bouncing around the room to be their malignant clones.
During this meeting, one overarching theme kept popping up: Evolution doesn’t operate the same way within all cancers. It’s not even clear that Darwinian natural selection always determines the genetic mutations that abound within a tumor. A study of colon cancer samples conducted by one of the conference attendees, Andrea Sottoriva of the Institute of Cancer Research in London, and Christina Curtis, a computational biologist at Stanford University, suggested a different pattern.
When colorectal tumors begin to form, there seems to be a “big bang” of mutations. This initial explosion of cellular diversity in these colon cancers seems to be followed by a period in which random genetic changes arise and become more prevalent out of pure happenstance rather than because the mutations confer some sort of competitive advantage. It’s still unclear whether adaptive therapy, which operates on the assumption that there’s Darwinian competition between tumor cells, would work well for cancers where the mutations arise continuously by chance.
Still, a kind of consensus emerged, and a year after the Cambridge meeting, the organizers published a statement outlining how cancers might be better classified. Twenty-two researchers—some of the biggest names in the field of evolutionary oncology, including Gatenby—coauthored the document.
One important factor in the group’s suggested classification scheme is a measure of how swiftly a cancer is mutating. In the past decade, faster DNA sequencing tools have shown that Nowell—Gatenby’s old professor, the cigarette-smoking pioneer in applying evolutionary thinking to cancer—was prescient: Individual tumors often bristle with rapid-fire genetic changes. Rather than two or three initial errors setting off a chain of uncontrolled growth, many tumors are the result of several series of mutations. A significant experiment published in 2012 found at least 128 different DNA mutations in various kidney tumor samples from one patient, for instance. There's some evidence that the more mutations there are, the more aggressive a cancer tends to be, suggesting a higher chance that one of these DNA changes will confer tumor cells with the potential to be drug-resistant. Given technological advances, it’s not too far-fetched to think that within the coming decade, doctors will routinely measure the amount of mutations in their patients’ tumors.
Today most cancers are assessed using a system that dates back to the 1940s. Doctors typically evaluate factors such as whether a cancer has spread to lymph nodes or beyond and on the basis of these attributes determine its “stage.” On one end of the spectrum are stage 1 cancers, which are relatively confined, while at the other end are stage 4 cancers, which have spread extensively. Crucially, this system of assigning cancer a stage doesn’t formally take a cancer’s genetic mutations into account.
The suggested categorization system that grew out of the Cambridge meeting would look at cancer in a completely new way. Rather than four stages of cancer, the authors of the 2017 consensus statement propose no less than 16 different categories—for example, tumors that have slow cell turnover and a low rate of accumulating mutations, or tumors that are a hotbed of genetic diversity with quickly replicating cells competing for resources. This latter type of tumor might be the most likely to evolve a way to outcompete drug-sensitive cells in the body and thereby could, in some cases, be the most dangerous. A fast-moving cancer of this kind might also be the best candidate for adaptive therapy.
Around the time the consensus statement came out, Gatenby and his collaborators in Tampa were hard at work running cell experiments in a lab down the hall from his office. The goal was to prove a key tenet of adaptive therapy. Gatenby’s approach assumes that when treatment is removed, drug-resistant cancer cells will replicate more slowly than drug-sensitive cells. The theory rests on the assumption that those resistant cells need lots of energy to maintain their armor against the medication meant to kill them. During treatment breaks, the thinking goes, the fuel-hungry resistant cells are outcompeted by drug-sensitive cells, which need fewer resources to thrive.
To gather evidence for this idea, Gatenby’s research team placed human breast cancer cells with resistance to the drug doxorubicin in a petri dish alongside an equal-size population of doxorubicin-sensitive breast cancer cells and watched the two groups fight for resources. By day 10 the resistant cells made up only 20 percent of the cells in the dish and continued to slowly decline from there. At the end of the experiment, published last year, these resistant cells had dropped to around 10 percent of the total population.
Granted, this experiment happened in a petri dish, not a human body—or even the body of a lab rat. Some leading cancer specialists agree with Gatenby that drug-resistant cells are likely outcompeted by other cells when cancer medication is withdrawn. But, say others, what if Gatenby is wrong? What if resistant cells actually thrive during the period when the patient is taken off drugs? The risks are high. No one wants to hasten death.
Rethinking cancer as a chronic illness requires a mental shift—a shift that other changes in cancer therapy might be easing. There’s a practice of letting cancer patients take doctor-supervised “drug holidays” from their medications, for instance. And we’ve adapted our thinking when it comes to medicine before. Doctors once thought that stress was the primary culprit behind ulcers, but biologists uncovered a bacterium as the main cause. More recently we’ve gotten used to the weird idea that trillions of bacteria live in our gut microbiome.
Perhaps, then, it isn’t a huge stretch to think we might tolerate coexisting with cancer cells as long as we can prevent them from growing unchecked. Whereas Darwin put forth ideas about what has become known as macroevolution—the rise and fall of species, whether they be beetles or bald eagles—this new view of cancer could be an example of what we might call “endo-evolution”: natural selection playing out within an organism’s own tissues.
The American Cancer Society acknowledges that some cancers are already managed as chronic illnesses. In certain cases, doctors simply try to keep the malignancies from spreading with new rounds of medication. Gatenby’s adaptive therapy aims to take the guesswork out of the treatment. More trials at Moffitt are in the planning stages or underway for cancers affecting the breast, skin and thyroid, in addition to a new, bigger trial in prostate cancer patients. Across the country, in Arizona, Athena Aktipis and her husband and scientific collaborator, Carlo Maley, have secured a grant to begin a breast cancer trial using adaptive therapy in conjunction with a local branch of the Mayo Clinic.
But the idea of cancer as an implacable enemy that needs to be annihilated runs deep. Even Gatenby feels it, particularly when it comes to children. When his daughter was a teenager, one of her classmates died from a form of cancer called rhabdomyosarcoma. He never met his daughter’s friend but heard about his decline. Then, last year, a pediatric oncologist at Moffitt approached him to see if therapy inspired by evolutionary theory might work to fully weed out cancer from children newly diagnosed with that same disease. In the highest-risk group, that cancer kills as many as 80 percent of patients within five years.
In October, they met to begin designing a study. This trial will use a more sophisticated evolutionary model to cycle patients on and off of several drugs. The hope is to deploy the additional drugs to kick the cancer while it’s down, and thereby drive it to extinction. It’s an ambitious goal.
For now, Gatenby is most focused on managing advanced cancers in adults, and doing so as a chronic disease. In that sense, he’s challenging the words emblazoned on the outside wall of the Moffitt Cancer Center: “To contribute to the prevention and cure of cancer.” Robert Butler has pondered these words too, which he passes when walking into the building for checkups and treatments. “Certainly, in my case there’s no intention of cure. What we’re doing is control. So that’s not really the correct logo anymore, is it?” he says. Butler tells me about a time when he and some of the Moffitt researchers brainstormed alternative slogans. “We finally came up with ‘Our aim is to make you die of something else’—which I thought was lovely,” he adds. “It’s more true.”
Robert Gatenby photographed at Everson Museum of Art
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Dressed in pastel pink and green for an early spring day, second-grader Katherine Cribbs was learning about energy on a virtual field trip—to her own school.
With a flurry of touch-screen taps, she explored the “energy dashboard” of Discovery Elementary in Arlington, Virginia. On her tablet, she swiped through 360-degree views of her school, inside and out. She clicked on icons embedded in the virtual classroom to learn about energy-saving features such as LED lights and super-insulated exterior walls made of concrete-filled foam blocks. Exploring the virtual school kitchen, she could read about how the lack of a deep fryer means less energy is needed for venting grease from the air. Another swipe whisked her up to the school’s roof, where about 1,700 solar panels spread out before her.
After a few minutes, she looked up from her computer to explain her progress in a confident voice that rose above the second-grade din. “I learned that our solar panels rotate,” she said. “So, wherever the sun moves, the panels go, too.”
In addition to this virtual tour, Discovery’s dashboard displays, in real time, the school’s energy generation. And in colorful bar graphs and pie charts, it also tracks energy use—broken down by lighting, plug load, kitchen, and HVAC. The tally reveals that Discovery generates more energy through its solar array than it uses over the course of the year.
Buildings that make at least as much energy as they use are called “net-zero” (and “net positive” if they make more than they need). And nationwide, K-12 schools are leading a fledgling “net-zero” building boom that has grown from a few proof-of-concept structures a decade ago to hundreds of buildings completed or under-construction.
Dozens of these ultra-green schools are going up in every sort of district—urban and rural, affluent and lower income, blue state and red state. Much of the advocacy for net-zero buildings has focused on environmental and economic incentives. K-12 schools run up a $6 billion annual energy tab every year, the Department of Energy reports—more than they spend on textbooks and computers combined, and second only to the cost of teacher salaries. But the K-12 schools leading the net-zero charge are uncovering major educational benefits as well.
While Discovery’s second-graders scoured their school for light and heat energy, a group of third graders huddled around a table to brainstorm fraction “story problems” using the school’s energy data.
They suggested using fractions to find out how much of yesterday’s solar energy was used up by the school, to compare one hour’s solar energy to the whole day, and to show how much of the school’s energy use was from lighting. Their numerators and denominators could come from the dashboard.
“Everywhere you walk through this building, you can learn from it,” said Discovery’s principal, Erin Russo. There’s a large-screen energy dashboard by the school’s main entrance, and the building’s mechanical systems, including the geothermal pumps and the solar inverters that change direct current to alternating current, are prominently displayed behind large glass windows in the hallway.
Learning about the behavior of light, Discovery’s fifth graders have visited the schools’ rooftop solar lab (a handful of adjustable panels that are metered separately) to see how angling the panels changes their power production.
“Energy is normally so invisible,” said a fifth-grade science teacher, Andrew Bridges. “But the kids can see these solar panels right outside their window. They can see the energy production dipping on cloudy days.”
Bridges’ students also looked for patterns of electricity use and tried to deduce why it was so much heavier on Saturdays than Sundays or why it spiked at 5 AM. “I didn’t give them energy-dashboard tests, because that’s not what we’re after,” said Bridges. “My goal as a teacher is to grow good critical thinkers, and I think the energy dashboard opens their eyes to something most people don’t think too much about.”
Still, Discovery’s teachers do need to cover the Virginia state learning standards, and matching these standards with dashboard lessons can be tricky. At one point, third graders were set to learn graphing with the school’s daily energy tally, but the plan was scrapped because the dashboard gives that data in bar graphs. Virginia’s third-grade standards call for using line graphs to track change over time.
Discovery’s math coach, Angela Torpy, and technology coach, Keith Reeves, help teachers weave the building’s data into standards-based lessons. Students learn the statistical measures of mean, median, and mode using the school’s energy consumption numbers, or demonstrate transparency, translucency, and opacity by covering solar panels with different materials and predicting the energy production.
Besides aligning with state standards, Discovery teachers must also contend with the dashboard’s occasional technical glitches—it tends to conk out due to server strain if too many kids are working on it. So teachers usually have students team up or rotate so one group hops on the dashboard while the rest of the class works on other tasks. Or they simply distribute screen grabs of dashboard data.
Still, according to Torpy, the upside of students learning from their own building outweighs these challenges. “You can see their level of excitement when they bring up the energy dashboard, and they’re making their own word problems with real data about their own school,” Torpy said of the students. “It’s empowering to them.”
The authenticity of these lessons is reinforced by a schoolwide focus on sustainability. In lieu of a school council, Discovery has an Eco-Action club whose members do annual audits of the school’s energy use, trash, food waste, water consumption, and other metrics. They did the school energy audit early in the school year, explained a fifth-grade Eco-Action member named Charlie Dantzker. “Basically, we walked into every classroom, counted the lights, checked to see what was plugged in, and looked for vampires,” Dantzker said. A vampire, he explained, is a device that draws power even when it’s turned off but still plugged into the wall.
But the students didn’t find a lot of waste in the audit: Discovery is already ultra-energy efficient. The school’s “energy use index,” a measure of power use per square foot, is about a third of the average for district elementary schools. The district plans to build on that success.
Arlington is a fast-growing district, and Discovery Elementary opened in 2015 as part of an ongoing school-building program (it shares a campus with a middle school with a trailer park to accommodate its overflowing student population). Below the schools’ shared athletic fields are geothermal wells that use a groundwater loop to provide cooling in summer and heat in winter.
The district had not set out to build a net-zero school, but the Charlottesville architecture firm VMDO told them it could be done below their budget. Cathy Lin, the energy manager for Arlington Public Schools, regularly leads tours of Discovery, including a rooftop viewing of its 500-kilowatt solar array made up of about 1,700 panels. Another net-zero elementary school, also designed by VMDO, is to open in 2019. And as the district keeps growing, Lin is pushing for more.
“I tell the board [of education] if I had all Discoveries, I would spend less than $1 million [a year] on utilities. Now, we spend close to $7 million a year,” she said.
This calculus increasingly makes sense to growing public school districts, according to Ralph DiNola, CEO of the New Buildings Institute, a nonprofit that promotes and verifies net-zero buildings. Because schools are designed to be used by the same owner over many decades, there is plenty of time for energy savings to surpass the extra upfront expenditures, which in any case have plummeted in the past decade. The cost of solar power is way down, and, according to DiNola, the necessary energy efficiency, “doesn’t require bleeding-edge technology. You can use standard building materials that are commonplace in the market today.”
Comparing the initial cost of building a net-zero school to that of a standard school is tough, because construction costs vary widely as do the energy-efficiency challenges between climates One constant, however, is that the priciest piece of a net-zero building is the solar array. For instance, Discovery’s construction cost for the building and the solar array came to about $316 per square foot, but the building alone cost $262 per square foot, according to VMDO architect Wyck Knox, who led the project design team (numbers don’t include the cost of the school’s two turf soccer fields). Often, districts will opt to build ultra-energy-efficient “net-zero ready” schools that could become net-zero if and when the municipality raises additional money to add the solar power.
According to a March 2018 NBI report, there are 89 verified or “emerging” net-zero schools (emerging means under construction or too new to have been verified yet). And school buildings are the leading type of non-residential net-zero building, representing 37 percent of all projects tracked by NBI. Supporting these efforts, the Department of Energy published a how-to report on building net-zero K-12 schools in 2016 and created a “Zero-Energy Schools Accelerator” program to give districts technical guidance.
While the net-zero school trend is still relatively small, it has thrived in districts of every geographic and socioeconomic description. The school district of Horry County, South Carolina, which counts the majority of its 43,800 students as impoverished, opened three net-zero schools in 2017, one in 2018, and has one more under construction. In San Francisco Unified, where half the students receive free and reduced-price lunch and a quarter are English language learners, the district is building three net-zero schools, including one retrofit of an existing elementary school. At Sandy Grove Middle School, a net-positive building in Hoke County, North Carolina, where nearly 60 percent of students are low-income, the grade levels face off in friendly energy-saving competitions. And at New York City’s first net-zero school, the Kathleen Grimm School for Leadership and Sustainability (P.S. 62) on Staten Island, rows of yellow stationary bikes, both indoors and on the playground, generate pedal power displayed on a big screen.
Although energy dashboards are a popular way to turn these buildings into teaching tools, they’re not necessary. Oregon’s Hood River Middle School created a food and conservation science program several years ago after it added a net-zero science and music building that includes a 1,000-square-foot greenhouse. Hood River students engineer and build net-zero heating and cooling systems for the greenhouse, such as solar heat collectors made of foam boxes lined with soda cans spray-painted black, and a solar-powered “climate battery” that pulls super-heated summer air into layers of dense rocks that gradually radiate the heat back into the greenhouse as the weather cools.
In addition to maintaining an aquaculture system and growing fruit trees, grapes, tea and other crops, the Hood River students have a perennial challenge from their teacher Michael Becker: to grow tomatoes year-round. They haven’t quite succeeded, but they’re getting close. Last year, they had tomatoes ripening on the vine well into December.
“My lesson plan is: Here’s a problem. Solve it,” said Becker. “We are hyper-aware of our net-zero energy budget, so the kids have to become super-sharp engineers and find non-traditional solutions.”
Back at Discovery, educational strategies are expanding, too. Last year’s school management plan included the expectation that teachers give at least one sustainability-focused lesson every quarter—but several teachers described that as a low bar.
“We’re shooting for sustainability to be taught every day,” said Bridges, the fifth-grade teacher. To bolster those efforts, Reeves is making changes to the energy dashboard, trying to add in student-collected data on the school’s trash production, water use, and transportation. The teachers would also like to make it easier for students to get the raw data that feeds the existing dashboard, so they could make their own, customized dashboards, possibly in conjunction with Virginia’s new K-12 computer science standards.
In the spring of 2018, Discovery staff began a more comprehensive effort to craft standards-based sustainability lessons, by working with Jennifer Seydel, executive director of the Green Schools National Network. Discovery will join GSNN’s recently-formed “Catalyst Network”—about 100 schools that are meant to showcase the best-practices in sustainability education and to jump-start studies into how it stacks up against traditional schooling for student learning.
“Right now, we have a lot of anecdotes,” said Seydel, “but the gold-standard research is not there.”
Starting in 2019, the plan is for all students to do sustainability audits, not just the Eco-Action club. Each grade level will use their audits to identify problems and issues they can confront with collaborative mastery projects using the problem-solving steps of “design thinking.”
Discovery art teacher Maria Burke has already led her students through several design-thinking projects, such as creating outdoor sculptures with the right mix of shapes and colors to attract pollinators back to a school garden that fell victim to overzealous pruning.
“We want to give students the skills to be innovators, to find solutions,” said Burke. “We want to them to be thinkers for the future and to collaborate and innovate with the world in mind.”
This story about environmental education was produced by The Hechinger Report, a nonprofit, independent news organization focused on inequality and innovation in education. Sign up for our newsletter.
Silke Weinfurtner is trying to build the universe from scratch. In a physics lab at the University of Nottingham—close to the Sherwood forest of legendary English outlaw Robin Hood—she and her colleagues will work with a huge superconducting coil magnet, 1 meter across. Inside, there’s a small pool of liquid, whose gentle ripples stand to mimic the matter fluctuations that gave rise to the structures we observe in the cosmos.
Weinfurtner isn’t an evil genius hell-bent on creating a world of her own to rule. She just wants to understand the origins of the one we already have.
The Big Bang is by far the most popular model of our universe’s beginnings, but even its fans disagree about how it happened. The theory depends on the existence of a hypothetical quantum field that stretched the universe ultra-rapidly and uniformly in all directions, expanding it by a huge factor in a fraction of a second: a process dubbed inflation. But that inflation or the field responsible for it—the inflaton—is impossible to prove directly. Which is why Weinfurtner wants to mimic it in a lab.
If the Big Bang theory is right, the baby universe would have been created with tiny ripples—so-called ‘quantum fluctuations’—which got stretched during inflation and turned into matter and radiation, or light. These fluctuations are thought to have eventually magnified to cosmic size, seeding galaxies, stars, and planets. And it’s these tiny ripples that Weinfurtner wants to model with that massive superconducting magnet. Inside, she’ll put a circular tank, some 6 centimeters in diameter, filled with layered water and butanol (the liquids have different densities, so they don’t mix).
Then, her group of researchers will kick in the artificial gravity distortions. “The strength of the magnetic field varies with its position,” says Richard Hill, one of the paper’s co-authors. “By moving the pool to different regions of the field, the effective gravitational force can be increased or decreased,” he says, “and can even be turned upside-down.”
By varying gravity, the team hopes to create ripples—but unlike those on a pond, the distortions will appear between the two liquids. “By carefully adjusting the speed of the ripples we can model an inflating universe,” says another team member, Anastasios Avgoustidis. In cosmic inflation, space rapidly expands while the ripples of matter propagate at a constant speed—and in the experiment, the speed of the ripples rapidly decreases as the liquid’s volume remains constant. “The equations describing the propagation of ripples in these two scenarios are identical,” Avgoustidis says.
That’s important: If the resulting fluctuations look as if they might trigger structures like those found in today’s universe, then we may have had a glimpse of how inflation worked.
This isn’t the first time Weinfurtner—or anyone else—has tried to mimic cosmic phenomena on a tiny scale. Around the world, astrophysicists can be found in labs, developing ever more sophisticated set-ups using sound waves that travel just like light waves in strong gravitational fields, or magnets to trigger perturbations in fluids and gases.
Last June, Weinfurtner used a large water tank with a sink in the middle to mimic another difficult-to-observe phenomenon: the superradiance of a black hole. And it was William Unruh, a physicist at the University of British Columbia in Vancouver (and Weinfurtner’s advisor a decade ago), who pioneered the idea of simulating gravity in a lab in 1981. After all, “we cannot rerun the universe—and cannot live long enough to see the results of the experiment if we could,” says Unruh.
Analog gravity experiments have gotten more sophisticated since Unruh’s first experiment, which used a fluid simulation of gravity to show that the event horizon of a real black hole does to light what a sonic black hole does to sound. In other words: What we can measure and express in the lab can be used to explore properties of astrophysical black holes. It even works for the famous Hawking radiation, the prediction that black holes radiate heat and at some point will totally evaporate. A few years ago, Jeff Steinhauer of the Technion in Haifa, Israel, discovered the radiation’s sonic analog.
Simulations are being used to study other aspects of inflation, too. A few years ago, a team led by Christoph Westbrook of CNRS (The French National Center for Scientific Research) in Paris studied the production of quantum particles by ‘wiggling’ a ring Bose Einstein condensate—a state of matter in which the atoms have been cooled to near absolute zero, making them behave as a single quantum object. During inflation, the temperature of the universe dropped drastically, before starting to rise again when the inflation ceased with the process called ‘reheating’—leading to the ordinary Big Bang expansion.
Another experiment last October, led by physicist Stephen Eckel at the Joint Quantum Institute at the National Institute of Standards and Technology and University of Maryland, also used a Bose Einstein condensate to observe the stretching of sound waves—analogous to the stretching, or redshifting, of light that happens as the universe expands. The team also observed an effect similar to the reheating process.
Weinfurtner says that her ‘novel’ setup can work without a Bose Einstein condensate. That means that the system will be too hot to observe quantum fluctuations directly, says Unruh. But the authors argue that it will be possible to observe the fluctuations via the thermal noise in their system—an analog of quantum noise.
Their approach, say the authors, will allow them to mimic a long expansion phase, achieving—using the technical language—‘many e-folds,’ a parameter that measures the duration of inflation. Researchers believe that inflation increased the size of the universe by more than a factor of 10^26—or more than 60 e-folds—in just a fraction of a second. The new experiment, if successful, would simulate inflation for much longer period than previous lab set-ups, or have “many more e-folds than any other, enough to put the results beyond doubt,” says Ian Moss of the University of Newcastle. “You need some time to elapse for the system to forget its initial conditions and settle down to the state governed by inflationary fluctuations,” he says.
“It is possible that they will uncover new physics that help to inform future cosmological models,” says Eckel. “Or, on the reverse, help to test some aspect of future cosmological models.”
Not everyone is convinced that simulating our universe’s first moments in the lab will help cosmology, though. Ted Jacobson of the University of Maryland thinks that such experiments are “not so much verifying something we are uncertain about, but rather implementing and observing it in a lab.” Why mimic the universe in the lab? “It’s fun. And it may suggest new phenomena we didn’t think of in cosmology,” he says.
Avi Loeb, an astrophysicist at Harvard University, is not as optimistic. He says that Weinfurtner’s proposed analogy of creating ripples between two fluids in a tank will not extend to the “fundamental physical nature” of quantum fluctuations—because the experiment simply reproduces the equations physicists already use to describe inflation. If these equations are missing a fundamental ingredient, the experiment will not reveal it. “While analog laboratory experiments could incorporate quantum mechanical effects, they do not involve the interplay of quantum mechanics with gravity in the way that black holes and inflation do," he says.
Weinfurtner’s experiment is tailored to reproduce our existing notion of inflation, Loeb adds – but it’s not meant to test it at a fundamental level. “The only way to get a discrepancy between the experiment and our notion of inflation is if we did the math wrong for one of these systems. Otherwise, we will learn nothing new,” he says.
The real test of inflation would be, Loeb says, the production of the substance that propelled it—the inflaton—in the lab. But this would require reaching energies up to a trillion times larger than those achieved in our most powerful particle accelerator, the Large Hadron Collider—and such a test seems unlikely in the near future.
“Just mimicking the equations of an analogous system is a metaphor to the real system, not an actual test of its fundamental properties,” says Loeb. It’s like “smelling food instead of eating the actual food,” he adds, only “the latter has the real value.”
That’s true, but sometimes the smells from a kitchen can tell you a lot about what was served for dinner.
Dan Hooper and his colleagues found a glow coming from the center of our galaxy that no one had ever noticed before—and it could hold new information about the universe.
For nearly a decade, Shami Chatterjee and other astrophysicists have been trying to understand the nature of fast bursts of radio waves in space.
Rachael Livermore uses the Hubble Space Telescope to spot extremely faint galaxies from as far back as 600 million years after the Big Bang.
The creation of Camp Century, from the outset, was an audacious scheme. Under the thick ice of Greenland, a scant 800 miles from the North Pole, the US military built a hidden base of ice tunnels, imagined as an extensive network of railway tracks, stretching over 2,500 miles, that would keep 600 nuclear missiles buried under the ice. Construction began in 1959, under cover of a scientific research project, and soon a small installation, powered by a nuclear reactor, nested in the ice sheet.
In the midst of the Cold War, Greenland seemed like a strategic point for the US to stage weapons, ready to attack the USSR. The thick ice sheet, military planners imagined, would provide permanent protection for the base. But after the first tunnels were built, the military discovered that the ice sheet was not as stable as it needed to be: It moved and shifted, destabilizing the tunnels. Within a decade, Camp Century was abandoned.
When siting the secret ice base, the military chose a spot where dry snow kept the surface of Greenland’s ice sheet from melting, and when the base was abandoned its creators expected the remains to stay encased in ice forever. But decades later, conditions have changed, and as a team of researchers reported in a 2016 paper, published in Geophysical Research Letters, the now-melting ice sheet threatens to mobilize the dangerous pollutants left behind.
This hazard-in-waiting is a new kind of environmental threat: In the past, there was little reason to worry about water-borne pollution on an ice sheet 100,000 years old. As Jeff D. Colgan, a professor of political science at Brown University, writes in an article released last week in the journal Global Environmental Politics, Camp Century represents both a second-order environmental threat from climate change and a new path to political conflict.
“We’re starting to get better about dealing with the anticipated problems associated with climate change,” says Colgan. “There are going to be a whole host of unanticipated problems that we never saw coming.”
By the time the base was abandoned in 1967, it had its own library and theater, an infirmary, kitchen and mess hall, a chapel, and two power plants (one nuclear, one run on diesel). When the base closed, key parts of the nuclear power plant were removed, but most of the base’s infrastructure was left behind—the buildings, the railways, the sewage, the diesel fuel, and the low-level radioactive waste. In the 2016 paper, which Colgan worked on as well, the researchers suggested that the radiological waste was less worrisome than the more extensive chemical waste, from diesel fuel and polychlorinated biphenyls (PCBs) used to insulate fluids and paints.
Overall, the researchers estimated that 20,000 liters of chemical waste remain at the Camp Century site, along with 24 million liters of “biological waste associated with untreated sewage.” That’s just at Camp Century; the military closed down bases at three other sites in Greenland, too, and it’s unclear how much waste is left there. Over the next few decades, the researchers found, melt water from the ice sheets could mobilize these pollutants, exposing both the wildlife and humans living in Greenland.
Creating these ice-bound military bases required a delicate political negotiation to begin with. The US established its bases in Greenland under agreement with Denmark, which governed the island at the time. (Greenland now has self-rule but is still part of the Kingdom of Denmark.) There were some principles outlined about the two governments’ responsibilities for the bases, but, as Colgan writes in the new paper, the status of American nuclear weapons on Greenland fell into a diplomatic gray area.
The Danish government had taken a stand against nuclear weapons and would never condone a nuclear base on Greenland. But in 1957, an American ambassador, Val Peterson, made an official overture to the Danish prime minister, H.C. Hansen. If—just say—the US had nuclear weapons in Greenland, would the Danish government want to know? Five days later, the prime minister had a response: “I do not think that your remarks give rise to any comments from my side,” he wrote, in a “informal, personal, top secret” paper. The US went ahead with the plan.
There was similar ambiguity around the responsibility for the physical assets of the base. While they remained the property of the United States, the agreement said they could be “disposed of” in Greenland, after input from the Danish government. But it’s not at all clear who’s responsible for dealing with a long-term environmental hazard posed by the waste abandoned there.
This problem—who will pay to clean up environmental waste—is a common one; in the US, the Superfund program assigns responsibility for a polluted site, often across multiple parties associated with it over the years. But in this sort of international agreement between two governments, there’s no parallel process for divvying up blame or costs.
“These agreements are rarely fully specified in what’s written down on paper. There’s no real procedure for addressing disputes,” says Colgan. “If Denmark says, US, you’re responsible, and the US says, no, you’re responsible—we don’t have a good resolution process for that. Climate change is likely to make that kind of problem a lot more common.”
Already, a Greenland politician, who was serving as foreign minister, has lost his job over this issue. After the 2016 paper came out, he started pushing for the US and Denmark to take responsibility for these military hazards; his boss thought he took too aggressive a stance.
But the problem isn’t going to go away, and Colgan emphasizes that these second-order environmental consequences of climate change—which he calls “knock-on effects”—are only going to become more common, creating knotty political disputes. Think, for instance, of the chemical and oil refineries that, damaged by Hurricane Harvey, started dumping waste.
Many of these environmental hazards, though, can be linked to multiple causes; in Greenland, it’s easier to pinpoint the precipitating issue.
“What’s helpful about Camp Century is that, because it’s so isolated, we can be really clear that what’s causing the problem is climate change,” says Colgan. In the 1960s, there was little reason for the US military to imagine that their secret ice-base would cause environmental problems decades in the future. After all, it was encased in ice and should only have been buried deeper into the frozen surface over time.
The tiny tadpole embryo looked like a bean. One day old, it didn’t even have a heart yet. The researcher in a white coat and gloves who hovered over it made a precise surgical incision where its head would form. Moments later, the brain was gone, but the embryo was still alive.
The brief procedure took Celia Herrera-Rincon, a neuroscience postdoc at the Allen Discovery Center at Tufts University, back to the country house in Spain where she had grown up, in the mountains near Madrid. When she was 11 years old, while walking her dogs in the woods, she found a snake, Vipera latastei. It was beautiful but dead. “I realized I wanted to see what was inside the head,” she recalled. She performed her first “lab test” using kitchen knives and tweezers, and she has been fascinated by the many shapes and evolutionary morphologies of the brain ever since. Her collection now holds about 1,000 brains from all kinds of creatures.
This time, however, she was not interested in the brain itself, but in how an African clawed frog would develop without one. She and her supervisor, Michael Levin, a software engineer turned developmental biologist, are investigating whether the brain and nervous system play a crucial role in laying out the patterns that dictate the shapes and identities of emerging organs, limbs and other structures.
For the past 65 years, the focus of developmental biology has been on DNA as the carrier of biological information. Researchers have typically assumed that genetic expression patterns alone are enough to determine embryonic development.
To Levin, however, that explanation is unsatisfying. “Where does shape come from? What makes an elephant different from a snake?” he asked. DNA can make proteins inside cells, he said, but “there is nothing in the genome that directly specifies anatomy.” To develop properly, he maintains, tissues need spatial cues that must come from other sources in the embryo. At least some of that guidance, he and his team believe, is electrical.
In recent years, by working on tadpoles and other simple creatures, Levin’s laboratory has amassed evidence that the embryo is molded by bioelectrical signals, particularly ones that emanate from the young brain long before it is even a functional organ. Those results, if replicated in other organisms, may change our understanding of the roles of electrical phenomena and the nervous system in development, and perhaps more widely in biology.
“Levin’s findings will shake some rigid orthodoxy in the field,” said Sui Huang, a molecular biologist at the Institute for Systems Biology. If Levin’s work holds up, Huang continued, “I think many developmental biologists will be stunned to see that the construction of the body plan is not due to local regulation of cells … but is centrally orchestrated by the brain.”
Bioelectrical Influences in Development
The Spanish neuroscientist and Nobel laureate Santiago Ramón y Cajal once called the brain and neurons, the electrically active cells that process and transmit nerve signals, the “butterflies of the soul.” The brain is a center for information processing, memory, decision making and behavior, and electricity figures into its performance of all of those activities.
But it’s not just the brain that uses bioelectric signaling—the whole body does. All cell membranes have embedded ion channels, protein pores that act as pathways for charged molecules, or ions. Differences between the number of ions inside and outside a cell result in an electric gradient—the cell’s resting potential. Vary this potential by opening or blocking the ion channels, and you change the signals transmitted to, from and among the cells all around. Neurons do this as well, but even faster: To communicate among themselves, they use molecules called neurotransmitters that are released at synapses in response to voltage spikes, and they send ultra-rapid electrical pulses over long distances along their axons, encoding information in the pulses’ pattern, to control muscle activity.
Levin has thought about hacking networks of neurons since the mid-1980s, when he was a high school student in the suburbs near Boston, writing software for pocket money. One day, while browsing a small bookstore in Vancouver at Expo 86 with his father, he spotted a volume called The Body Electric, by Robert O. Becker and Gary Selden. He learned that scientists had been investigating bioelectricity for centuries, ever since Luigi Galvani discovered in the 1780s that nerves are animated by what he called “animal electricity.”
However, as Levin continued to read up on the subject, he realized that, even though the brain uses electricity for information processing, no one seemed to be seriously investigating the role of bioelectricity in carrying information about a body’s development. Wouldn’t it be cool, he thought, if we could comprehend “how the tissues process information and what tissues were ‘thinking about’ before they evolved nervous systems and brains?”
He started digging deeper and ended up getting a biology doctorate at Harvard University in morphogenesis—the study of the development of shapes in living things. He worked in the tradition of scientists like Emil du Bois-Reymond, a 19th-century German physician who discovered the action potential of nerves. In the 1930s and ’40s, the American biologists Harold Burr and Elmer Lund measured electric properties of various organisms during their embryonic development and studied connections between bioelectricity and the shapes animals take. They were not able to prove a link, but they were moving in the right direction, Levin said.
Before Genes Reigned Supreme
The work of Burr and Lund occurred during a time of widespread interest in embryology. Even the English mathematician Alan Turing, famed for cracking the Enigma code, was fascinated by embryology. In 1952 he published a paper suggesting that body patterns like pigmented spots and zebra stripes arise from the chemical reactions of diffusing substances, which he called morphogens.
"This electrical signal works as an environmental cue for intercellular communication, orchestrating cell behaviors during morphogenesis and regeneration."
But organic explanations like morphogens and bioelectricity didn’t stay in the limelight for long. In 1953, James Watson and Francis Crick published the double helical structure of DNA, and in the decades since “the focus of developmental biology has been on DNA as the carrier of biological information, with cells thought to follow their own internal genetic programs, prompted by cues from their local environment and neighboring cells,” Huang said.
The rationale, according to Richard Nuccitelli, chief science officer at Pulse Biosciences and a former professor of molecular biology at the University of California, Davis, was that “since DNA is what is inherited, information stored in the genes must specify all that is needed to develop.” Tissues are told how to develop at the local level by neighboring tissues, it was thought, and each region patterns itself from information in the genomes of its cells.
The extreme form of this view is “to explain everything by saying ‘it is in the genes,’ or DNA, and this trend has been reinforced by the increasingly powerful and affordable DNA sequencing technologies,” Huang said. “But we need to zoom out: Before molecular biology imposed our myopic tunnel vision, biologists were much more open to organism-level principles.”
The tide now seems to be turning, according to Herrera-Rincon and others. “It’s too simplistic to consider the genome as the only source of biological information,” she said. Researchers continue to study morphogens as a source of developmental information in the nervous system, for example. Last November, Levin and Chris Fields, an independent scientist who works in the area where biology, physics and computing overlap, published a paper arguing that cells’ cytoplasm, cytoskeleton and both internal and external membranes also encode important patterning data—and serve as systems of inheritance alongside DNA.
And, crucially, bioelectricity has made a comeback as well. In the 1980s and ’90s, Nuccitelli, along with the late Lionel Jaffe at the Marine Biological Laboratory, Colin McCaig at the University of Aberdeen, and others, used applied electric fields to show that many cells are sensitive to bioelectric signals and that electricity can induce limb regeneration in nonregenerative species.
According to Masayuki Yamashita of the International University of Health and Welfare in Japan, many researchers forget that every living cell, not just neurons, generates electric potentials across the cell membrane. “This electrical signal works as an environmental cue for intercellular communication, orchestrating cell behaviors during morphogenesis and regeneration,” he said.
However, no one was really sure why or how this bioelectric signaling worked, said Levin, and most still believe that the flow of information is very local. “Applied electricity in earlier experiments directly interacts with something in cells, triggering their responses,” he said. But what it was interacting with and how the responses were triggered were mysteries.
That’s what led Levin and his colleagues to start tinkering with the resting potential of cells. By changing the voltage of cells in flatworms, over the last few years they produced worms with two heads, or with tails in unexpected places. In tadpoles, they reprogrammed the identity of large groups of cells at the level of entire organs, making frogs with extra legs and changing gut tissue into eyes—simply by hacking the local bioelectric activity that provides patterning information.
And because the brain and nervous system are so conspicuously active electrically, the researchers also began to probe their involvement in long-distance patterns of bioelectric information affecting development. In 2015, Levin, his postdoc Vaibhav Pai, and other collaborators showed experimentally that bioelectric signals from the body shape the development and patterning of the brain in its earliest stages. By changing the resting potential in the cells of tadpoles as far from the head as the gut, they appeared to disrupt the body’s “blueprint” for brain development. The resulting tadpoles’ brains were smaller or even nonexistent, and brain tissue grew where it shouldn’t.
Unlike previous experiments with applied electricity that simply provided directional cues to cells, “in our work, we know what we have modified—resting potential—and we know how it triggers responses: by changing how small signaling molecules enter and leave cells,” Levin said. The right electrical potential lets neurotransmitters go in and out of voltage-powered gates (transporters) in the membrane. Once in, they can trigger specific receptors and initiate further cellular activity, allowing researchers to reprogram identity at the level of entire organs.
This work also showed that bioelectricity works over long distances, mediated by the neurotransmitter serotonin, Levin said. (Later experiments implicated the neurotransmitter butyrate as well.) The researchers started by altering the voltage of cells near the brain, but then they went farther and farther out, “because our data from the prior papers showed that tumors could be controlled by electric properties of cells very far away,” he said. “We showed that cells at a distance mattered for brain development too.”
Then Levin and his colleagues decided to flip the experiment. Might the brain hold, if not an entire blueprint, then at least some patterning information for the rest of the body, Levin asked—and if so, might the nervous system disseminate this information bioelectrically during the earliest stages of a body’s development? He invited Herrera-Rincon to get her scalpel ready.
Making Up for a Missing Brain
Herrera-Rincon’s brainless Xenopus laevis tadpoles grew, but within just a few days they all developed highly characteristic defects—and not just near the brain, but as far away as the very end of their tails. Their muscle fibers were also shorter and their nervous systems, especially the peripheral nerves, were growing chaotically. It’s not surprising that nervous system abnormalities that impair movement can affect a developing body. But according to Levin, the changes seen in their experiment showed that the brain helps to shape the body’s development well before the nervous system is even fully developed, and long before any movement starts.
That such defects could be seen so early in the development of the tadpoles was intriguing, said Gil Carvalho, a neuroscientist at the University of Southern California. “An intense dialogue between the nervous system and the body is something we see very prominently post-development, of course,” he said. Yet the new data “show that this cross-talk starts from the very beginning. It’s a window into the inception of the brain-body dialogue, which is so central to most vertebrate life as we know it, and it’s quite beautiful.” The results also raise the possibility that these neurotransmitters may be acting at a distance, he added—by diffusing through the extracellular space, or going from cell to cell in relay fashion, after they have been triggered by a cell’s voltage changes.
Herrera-Rincon and the rest of the team didn’t stop there. They wanted to see whether they could “rescue” the developing body from these defects by using bioelectricity to mimic the effect of a brain. They decided to express a specific ion channel called HCN2, which acts differently in various cells but is sensitive to their resting potential. Levin likens the ion channel’s effect to a sharpening filter in photo-editing software, in that “it can strengthen voltage differences between adjacent tissues that help you maintain correct boundaries. It really strengthens the abilities of the embryos to set up the correct boundaries for where tissues are supposed to go.”
To make embryos express it, the researchers injected messenger RNA for HCN2 into some frog egg cells just a couple of hours after they were fertilized. A day later they removed the embryos’ brains, and over the next few days, the cells of the embryo acquired novel electrical activity from the HCN2 in their membranes.
The scientists found that this procedure rescued the brainless tadpoles from most of the usual defects. Because of the HCN2 it was as if the brain was still present, telling the body how to develop normally. It was amazing, Levin said, “to see how much rescue you can get just from very simple expression of this channel.” It was also, he added, the first clear evidence that the brain controls the development of the embryo via bioelectric cues.
As with Levin’s previous experiments with bioelectricity and regeneration, many biologists and neuroscientists hailed the findings, calling them “refreshing” and “novel.” “One cannot say that this is really a step forward because this work veers off the common path,” Huang said. But a single experiment with tadpoles’ brains is not enough, he added — it’s crucial to repeat the experiment in other organisms, including mammals, for the findings “to be considered an advance in a field and establish generality.” Still, the results open “an entire new domain of investigation and new of way of thinking,” he said.
Levin’s research demonstrates that the nervous system plays a much more important role in how organisms build themselves than previously thought, said Min Zhao, a biologist at the University of California, Davis, and an expert on the biomedical application and molecular biophysics of electric-field effects in living tissues. Despite earlier experimental and clinical evidence, “this paper is the first one to demonstrate convincingly that this also happens in [the] developing embryo.”
“The results of Mike’s lab abolish the frontier, by demonstrating that electrical signaling from the central nervous system shapes early development,” said Olivier Soriani of the Institut de Biologie de Valrose CNRS. “The bioelectrical activity can now be considered as a new type of input encoding organ patterning, allowing large range control from the central nervous system.”
Carvalho observed that the work has obvious implications for the treatment and prevention of developmental malformations and birth defects—especially since the findings suggest that interfering with the function of a single neurotransmitter may sometimes be enough to prevent developmental issues. “This indicates that a therapeutic approach to these defects may be, at least in some cases, simpler than anticipated,” he said.
Levin speculates that in the future, we may not need to micromanage multitudes of cell-signaling events; instead, we may be able to manipulate how cells communicate with each other electrically and let them fix various problems.
Another recent experiment hinted at just how significant the developing brain’s bioelectric signal might be. Herrera-Rincon soaked frog embryos in common drugs that are normally harmless and then removed their brains. The drugged, brainless embryos developed severe birth defects, such as crooked tails and spinal cords. According to Levin, these results show that the brain protects the developing body against drugs that otherwise might be dangerous teratogens (compounds that cause birth defects). “The paradigm of thinking about teratogens was that each chemical is either a teratogen or is not,” Levin said. “Now we know that this depends on how the brain is working.”
These findings are impressive, but many questions remain, said Adam Cohen, a biophysicist at Harvard who studies bioelectrical signaling in bacteria. “It is still unclear precisely how the brain is affecting developmental patterning under normal conditions, meaning when the brain is intact.” To get those answers, researchers need to design more targeted experiments; for instance, they could silence specific neurons in the brain or block the release of specific neurotransmitters during development.
Although Levin’s work is gaining recognition, the emphasis he puts on electricity in development is far from universally accepted. Epigenetics and bioelectricity are important, but so are other layers of biology, Zhao said. “They work together to produce the biology we see.” More evidence is needed to shift the paradigm, he added. “We saw some amazing and mind-blowing results in this bioelectricity field, but the fundamental mechanisms are yet to be fully understood. I do not think we are there yet.”
But Nuccitelli says that for many biologists, Levin is on to something. For example, he said, Levin’s success in inducing the growth of misplaced eyes in tadpoles simply by altering the ion flux through the local tissues “is an amazing demonstration of the power of biophysics to control pattern formation.” The abundant citations of Levin’s more than 300 papers in the scientific literature—more than 10,000 times in almost 8,000 articles—is also “a great indicator that his work is making a difference.”
The passage of time and the efforts of others carrying on Levin’s work will help his cause, suggested David Stocum, a developmental biologist and dean emeritus at Indiana University-Purdue University Indianapolis. “In my view, his ideas will eventually be shown to be correct and generally accepted as an important part of the framework of developmental biology.”
“We have demonstrated a proof of principle,” Herrera-Rincon said as she finished preparing another petri dish full of beanlike embryos. “Now we are working on understanding the underlying mechanisms, especially the meaning: What is the information content of the brain-specific information, and how much morphogenetic guidance does it provide?” She washed off the scalpel and took off her gloves and lab coat. “I have a million experiments in my mind.”
Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.
Don’t worry: Technology may come and go, but some things never change. In the not-so-distant future, cars will drive themselves and men may become obsolete (sorry, guys), but home will always be home. It’ll just be a heck of a lot smarter.
Granted, some tech is better than other tech. No one needs a Wi-Fi-connected juice press that doesn’t actually juice anything. Gadgets that offer real utility—like a smart oven or open source furniture—stand a better chance of becoming ubiquitous. If you’re skeptical, think of it this way: In-home refrigeration was the crazy, newfangled invention of 1913. Now, few among us can imagine living without it.
What will the home of the future look like? We took stock of the most exciting tech-forward home products on the market. It’s only a matter of time until at least some of these come standard in every American home.
The High-Tech Living Room
Thirty-nine million Americans now have a smart speaker in their homes—that’s 1 in 6 people—and all signs indicate this figure will only creep higher with time. In the living room of the future, smart speakers will be a central feature, with newer models connected to every element in your home, from the lightbulbs to the lock on your front door to the thermostat. They will become so essential you won’t think twice about plunking down $400 for one.
Watching TV and movies will be a wildly different experience. Why devote precious square footage in your living room to a giant screen when you could have one that effortlessly rolls up away and out of sight, like the one LG Display debuted at this year’s CES? Or you may choose not to have a TV at all and opt instead for a superhigh-resolution short-throw projector that turns any white wall into your own personal movie theater. Sony’s new $30,000 model would fit the bill, assuming the price tag comes down.
In the coming years, it’ll be much easier to design your living space. Apps and online platforms such as Modsy and Hutch will use virtual and augmented reality to help you visualize how a couch or chair will look in your home. You’ll have lots of options: Modular, open source furniture will dominate interior design trends, taking the lead from Ikea’s Tom Dixon-designed Delaktig couch, which has more than 97 different configurations. Choose wisely, because you’ll be spending more time on the couch than ever: Facebook Inc.’s forthcoming living-room-geared video chat device will reportedly use smart camera technology to make people on both ends feel like they’re sitting in the same room.
Also, expect your living room to be even more of a central hub than it already is. Deliveries will arrive here instead of on your front porch, thanks to Amazon.com’s new Prime service, which will let verified delivery persons carry goods right into your home.
And don’t for a minute think ultramodern gadgetry is only for the younger set: Homes for the elderly will be outfitted with internet-connected gear that allows adult children to monitor their aging parents.
Smart Cooking in the Kitchen
Ultimately, the goal of kitchen technology won’t be to do the cooking for you. It’ll just make you a better cook. Smart ovens such as those from June will be outfitted with cameras and digital thermometers, helping you monitor your food as it bakes. And instead of just hoping the “medium-hot” setting on your gas range is hot enough, smart skillets will take guessing out of the equation by sizzling food at a precise temperature, which you’ll set on a connected app.
Smart refrigerators will help reduce waste by letting you know when the carrots in your fridge are about to go bad, and offer up several recipes for them to boot. The smart fridge from LG will even send cooking instructions to your smart oven. Meanwhile, 3D food printers will help you create intricately shaped pasta, and smart-technology-equipped ice cream makers will automatically sense the hardness of the mixture within and keep it ready until it’s sundae time.
Tech Enters the Bedroom
The latest wave of home-focused technology is about making everyday life better and easier, and that begins with a good night’s sleep. Sleep trackers such as Eight’s smart mattress and smartphone apps Sleep Time and Sleep Cycle will use sensors to measure your sleep metrics, while smart alarm clocks like Amazon’s mini Echo will help you begin your day on the right foot with time, weather, and news.
Need a gentler wake-up? The smart aromatherapy alarm clocks from Nox Aroma will sense when you’ve reached your sleep cycle’s lightest point and release a wake-up scent of your choice.
Once you’re up and moving, it’s time to get dressed: Your closet will be filled with clothes you don’t just wear. They will actually interact with you, tracking health markers and habits. Among them: MadeWithGlove’s still-in-development smart gloves, which promise to detect skin temperature and provide heat accordingly. Your clothes might even change shape or color based on your feelings, as will the Sensoree mood sweater, now available for preorder.
And if you want a new wardrobe, you won’t have to even leave the house to find the best-fitting clothes: Amazon’s patented mirror will let you virtually try on outfits from the comfort of your own bedroom.
Yes, Even in the Bathroom
In the future, spa-like experiences at home will be the norm. No need to draw your own bath—your digital assistant can do that for you with smart shower systems like those from U by Moen. High-tech tubs such as those from Toto will induce relaxed brain waves, while nose-geared gadgets like Olfinity will let you program and control your own aromatherapy session from your iPhone while you soak.
Sound far-fetched? Remember a decade ago, few of us could have imagined being so attached to our smartphones, let alone ordering groceries off the internet or barking commands at a digital assistant. With time, even the strangest things can become normal.
In Daniele Abate’s Sicilian home town, many people don’t even have running water, and he blames the politicians. So the former cook will be voting for Five Star on March 4.
At the other end of the country, across the economic divide that runs through Italy, a third of small company owners in Vicenza plan to do the same, according to Luigino Bari, who runs a local business association. They want tax cuts and deregulation, he says.
As an uncertain country gears up for a crucial election, the anti-establishment Five Star Movement is demonstrating a rare ability to appeal to disaffected voters across geography and social strata. Its eclectic mix of environmentalism, euro-skepticism and widely questioned promises on taxes and benefits offers something for anyone with an ax to grind about the way Italy has been run.
“It’s a catch-all party,” said Piergiorgio Corbetta, a political science professor at the University of Bologna. “There are many reasons to vote for Five Star.”
With four weeks to go, polls show Five Star may have provided enough reasons to secure one of the biggest victories yet for populists in western Europe. With an outright majority still a distant prospect and few natural allies in parliament, the party is still likely to be kept out of office by an alliance of establishment groups. But their success highlights the challenge facing the next administration.
“Whatever color of government Italy ends up with, they will weigh heavily on the debate,” said Marc Lazar, a professor at Sciences Po in Paris. “When you take almost 30 percent of the vote, you are a reality that must be dealt with.”
Since starting as an internet-based campaign group in 2009, Five Star’s rise has been driven by support in places like Abate’s home region of Trapani, which was found to have the lowest quality of life among Italy’s 110 provinces by La Sapienza University last year.
Abate has been living off a 280-euro ($350) disability pension each month since his knee gave out a few years ago, forcing him to give up kitchen work. He’s 53, but looks older and struggles to stand. For Abate, the appeal of Five Star is its pledge to take on the privileges of lawmakers and civil servants in Rome.
“We work for many years and barely get a thing,” he said, sitting in the main square of his hometown of Alcamo near a 17th century church. “They serve for a few months and can retire.’’
The key to electoral success for Five Star leader Luigi Di Maio will be pushing into Italy’s wealthier north. While the party won 40 percent of the vote in Trapani in the last national elections 2013, it got 25 percent in the manufacturing center of Vicenza near Venice.
Vicenza’s entrepreneurs are also frustrated with the status quo, regardless of the recent pickup in growth. They are demanding cuts to business taxes and regulations, and investment in the single-lane roads crowded with trucks carrying products from the region’s factories.
“It’s clear that the traditional parties have made promises that they haven’t kept,” said Bari, 64, who wouldn’t say who he’ll be voting for.
Just down the road, the 7,000 inhabitants of Sarego elected the first Five Star mayor in the northeastern Italy in 2012. Roberto Castiglion, a 37-year-old IT manager, was re-elected last year with an increased vote.
Most of Castiglion’s work as mayor has involved the environment, installing solar panels and increasing recycling, but he says the party is very keen to help local businesses which ship factory machinery, adult diapers and leather goods around the world.
“In this country, we are drowning in norms and regulations,” he said.
“Five Star is saying the right things to small businesses, but there is some hesitancy,” said Remigio Bisognin, the 63-year-old founder of a 14-employee Sarego firm that stamps plastic parts. “We don’t really know these people.’’
One source of concern for business leaders has been Five Star’s past threats to pull Italy out of the euro. Bisognin says mistakes were made introducing the single currency but it’s too late to go back now, and Di Maio has walked back his comments. It’s a move that broadens the party’s appeal in the north without hurting its base in the south.
“The euro is not something we worry about,” said Gaetano Milazzo, a 40-year-old tax collector as he talked to friends where the warren of narrow streets opens out into Alcamo’s square. “Some houses here get water one day a week and there’s hardly any public transport.”
Indeed, parts of the sprawling town of 45,000 aren’t even connected to the water mains and Domenico Surdi, the 34-year-old lawyer Five Star mayor since in 2016, says the existing pipes hadn’t been maintained for decades when he took office.
With no budget for repairs, Surdi has had to improvise. He’s aiming to raise the amount of garbage that’s recycled to 70 percent from about 60 percent to save about 1 million euros a year on trash hauling.
“We’ve been mismanaged for so long,” said Abate. “The problems won’t go away overnight.”
The long read: Scientists have identified 2 million species of living things. No one knows how many more are out there, and tens of thousands may be vanishing before we have even had a chance to encounter them
The Earth is ridiculously, burstingly fullof life. Four billion years after theappearance of the first microbes, 400myears after the emergence of thefirst life on land, 200,000 years after humans arrived on this planet, 5,000 years (give or take) after God bid Noah to gather to himself two of every creeping thing, and 200 years after we started to systematically categorise allthe worlds living things, still, new species are being discovered by the hundreds and thousands.
In the world of the systematic taxonomists those scientists charged with documenting this ever-growing onrush of biological profligacy the first week of November 2017 looked like any other. Which is to say, it was extraordinary. It began with 95 new types of beetle from Madagascar. But this was only the beginning. As the week progressed, it brought forth seven new varieties of micromoth from across South America, 10 minuscule spiders from Ecuador, and seven South African recluse spiders, all of them poisonous. A cave-loving crustacean from Brazil. Seven types of subterranean earwig. Four Chinese cockroaches. A nocturnal jellyfish from Japan. A blue-eyed damselfly from Cambodia. Thirteen bristle worms from the bottom of the ocean some bulbous, some hairy, all hideous. Eight North American mites pulled from the feathers of Georgia roadkill. Three black corals from Bermuda. One Andean frog, whose bright orange eyes reminded its discoverers of the Incan sun god Inti.
About 2m species of plants, animals and fungi are known to science thus far. No one knows how many are left to discover. Some put it at around 2m, others at more than 100m. The truescope of the worlds biodiversity is one of the biggest and most intractable problems in the sciences. Theres no quick fixor calculation that can solve it, just a steady drip of new observations of new beetles and new flies, accumulating towards a fathomless goal.Read More