Bob and Sue Ritter are looking cleaned and pressed, but deep in their bodies, from the base of the brain to the hormones of the gut, they’re feeling the after-effects of five days in the wilderness. They walked 30 miles with packs, encountering thousands of feet of elevation, windfalls, and part of a day lost to figuring out where they were besides Somewhere on the Bitterroot Divide.
“The person we were with described it as walking on air,” says Sue, “because up at the very, very top, at the divide, we were at the highest elevation around and you could see everywhere, in both directions.”
“It’s kind of like a knife’s edge,” says Bob.
The payoff came in spectacular views of Montana and Idaho and visits to catch-and-eat alpine lakes.
Still, Bob came back five pounds lighter. Craving something salty and rich, they ate pizza.
Now, as they pull up chairs in the din of Pullman’s Black Cypress, a Mediterranean feast beckons in foreign, palate-tempting words: tsatsiki, briam, skordalia, ratatouille, ciabatta, plus the fundamental food groups: oil, garlic, vinegar, Merlot, and India Pale Ale.
Beth DeWeese, my charming and intelligent bride of 27 years, poses a question:
“Do appetizers really stimulate your appetite? They just get me full.”
“I think they’re something to do while you’re waiting,” says Bob. “Animals”—and by this he means other, non-human animals—“don’t eat appetizers.”
Sue counters with a friendly rebuttal.
“Sometimes something good or something you eat for your regular meal can stimulate insulin release,” she says. “And if you haven’t eaten for a while, that insulin release can actually potentiate your appetite.”
This is what can safely be called an Expert Opinion. And so it is resolved: We will get appetizers.
Everyone eats. We obsess over eating. We know we should have several servings of fruit and vegetables each day but can’t avoid chips, be they potato, tortilla, or fish ’n’. In some form or other we repeat the mantra my Danish-New Jersey mother uttered for four decades of Sundays: Tomorrow we’re all going on a diet.
But for all our obsession, we know little about the science of what’s going on, neither why we eat—and it’s not just because we’re hungry—nor why we stop eating—and it’s not just because our stomach is full.
Few people have plumbed these mysteries like the Ritters. Since the 1970s, they have carved out a tidy niche in which she specializes in appetite and he specializes in satiation. They’ve broken a lot of ground along the way, often with the adventurous attitude that has otherwise reasonable people tightrope across country that nearly defeated Lewis and Clark. When they arrived at WSU, eastern colleagues dismissed it as the “unwashed West” and their startup package was little more than a few cans of paint for an animal room.
“I think they also gave us some animal traps for the wildlife coming up the drain,” says Sue. She was only the second female faculty member at the WSU vet school. By then, she had already encountered her fair share of students and faculty who felt she was in the wrong job for a woman.
Both of them flourished with a creativity, freedom, and eclecticism that is reflected in their two sons. Lincoln, 30, set out to be a jazz musician, studied physics and math, and became a computer engineer. Josh, 34, majored in biology, then turned his attention to singing and songwriting. After seven albums, headlining with Joan Baez, comparisons to Bob Dylan, Bruce Springsteen, and Leonard Cohen, and an appearance on Letterman, he calls his parents “the single greatest influence on my music.”
In an email interview, he recalls a quote his mom has on her windowpane, that “we should see what everyone else has seen and think what no one else has thought.”
“It always felt like a challenge that was worth taking up,” he says. “They also find their inspiration, as all artists do, in places and things that might be very far removed from the laboratory. They know that inspiration can come from anywhere and they work hard to continually satisfy their curiosities. This extends to miniature donkey upkeep, Habitat for Humanity, Biblical archaeology, muralling, mosaic work, backpacking, and traveling all over the world.”
The Ritters’s main métier is the inner workings of the brain, the most complicated and spectacular organ on the planet.
Josh, who in high school and college worked and published with his mom, calls it, “the terrifyingly vast universe that swirls away between our ears.”
“To study the brain is to stand on the deck of a ship and look out at a new and unmapped continent,” he says. “All you can see is thick jungle all the way down to the water’s edge. It’s like nothing you’ve ever seen before—overgrown, tendriled, populated by mysteries. Then your mom and dad jump over the edge of the ship and swim ashore with a pen and a microscope and set about dauntlessly to try and understand everything they can.”
More specifically, they look at the rat brain, which weighs all of two grams and barely covers a man’s thumbnail. Bob in particular has focused on a part of the brain largely overlooked by other neurologists, charting neurons and pathways between the hindbrain and parts of the gut. Their world is far removed from Medium Raw and The Belly Fat Cure but it’s the kind of work that stands to uncover the real reason diets don’t work, or why we lean towards obesity, why we crave certain foods, or why a diabetic can fail to recognize a fatal dose of insulin.
In some ways, their work is brain surgery, writ small but scalable to the human level and in a realm that is pretty much the most important thing in animal existence.
“If you look back on evolution,” says Sue, “all your important sensory systems are right by your mouth.”
Yes, love makes the world go ’round and for many of us the dollar is almighty, but our need for food holds sway over our daily activities, from when we wake up to how we move about in our world.
Consider the object lesson of so many marathoners and anorectics who stop ovulating because they are low on glucose, the essential energy source for the brain and a fundamental fuel for the rest of the body. Reproduction is important, the fundamental act of a species perpetuating itself. But first, we eat.
Appetite for Knowledge
Sue and Bob Ritter are the embodiment of curiosity, constantly shooting the gap between what they know and what they want to know.
Sue Ritter was that way back on Roxy Ann, a small mountain just outside the southern Oregon town of Medford. The family had no television. She spent her childhood hiking and riding bareback, pretending to be an Indian, finding favorite trees. For hopscotch tokens she used shiny pieces of glass and ceramic that she’d pull from pack rat middens. She gave little thought to science at the time, but was loaded with questions and challenged by her father to wonder about the ages of rocks and origins of stars.
“He was a very imaginative kind of person and really encouraged me,” she says one morning in her Wegner Hall office. “And he encouraged me in ways that I thought were very unusual for the time. He didn’t want me to feel constrained by the fact that I was a girl and that there were certain things that girls should do and certain things they shouldn’t.”
At Valparaiso University in Indiana, where she studied psychology, she met a kindred spirit in Bob, a Pennsylvania native given to searching under rocks and collecting moths, butterflies, reptiles, and amphibians. Sue took part of her junior year off to work as a United Airlines flight attendant. They married the day after he graduated. When he went for a doctorate in veterinary medicine
at the University of Pennsylvania, she followed, finishing her last undergraduate semester in absentia and taking a time-slip job in the lab of Penn neurologist Richard Harner.
She helped Harner study sleep cycles in cats—cleaning cages, analyzing electroencephalograms, helping with surgeries. He gave her Marie Curie’s biography and encouraged her to read scientific journals. Moreover, he showed her that she could design experiments to help answer questions about the brain.
“That opened an area of thought for me.”
At Harner’s suggestion, she applied to the Penn psychology department.
“The chairman of the department at that time said openly to my face, ‘I don’t even want to look at your application,’” she recalls. “And he says, ‘We’re not taking women because women don’t stay in the field.’” There were more slights to come, including WSU vet students who complained that it was hard to take a pregnant professor seriously, but she was unbowed.
She went to Bryn Mawr, a women’s school, doing more work on cats for her master’s. For her doctorate, she focused on hindbrain catecholamine neurons—brain cells in the brain’s reward and motivation circuitry—and today studies their role in controlling food intake and metabolism. She took some classes at Penn, and a neuroscience class she attended interested Bob in the field. The teacher, Alan Epstein, became his doctoral advisor and her adoptive mentor. Epstein paid their way to the first meeting of the Society for Neuroscience in 1971. They remember only a few hundred people. The society’s 2009 meeting had more than 30,000 attendees.
Two co-authored books, and more than 100 papers each later, they’re still curious and probing.
“Your answer is never the final answer and the truth you find is only a temporary truth,” says Sue. “You always need and want to move beyond that to the next step. And the next step not only points you ahead but it reinterprets often what you have already found. It’s a very complex thing. You’re in the midst of an enveloping cloud of curiosity that looks ahead and looks back at the same time. You find this common path between what you found before and what you’re moving ahead to.”
“A lot of the hypotheses that you generate and form, you quickly disprove and have to discard,” says Bob. “So in a way it’s a lot like turning over rocks. There’s nothing under most of them. But when you do find something, it’s exciting. And I often wonder why more scientists aren’t compulsive gamblers.”
Enter Food: Delicate, charred lamb chops, scallops with sliced garden zucchini, a piece of salmon, a pork chop fit for Fred Flintstone. Hungry, we dig in.
In the case of Bob and the lamb chops, this is an act as simple as eating with one’s hands. But it’s complicated. As Sue told me on an earlier occasion, much of our behavior is organized around food, with a lot of factors determining when we eat: food’s availability and tastiness, when we want to eat, social situations, habits. All these factors promote eating when food is available and storing the excess as fat or glycogen, the main way we hold on to glucose.
Sue herself has focused on the relatively fundamental act of how the brain reacts when it senses it might be low on glucose.
A brain needs to be small, if only to get a newborn’s head through the birth canal. It can’t be cluttered up with stored energy and water.
At the same time, the brain absolutely, positively has to have glucose. Two, three minutes without it, it’s over. So glucose storage gets subcontracted to other parts of the body and the brain uses an elaborate supply-chain management system for guaranteed, always-on-time delivery. In times of need, it can tap storage sites, temporarily raising glucose in the blood bound for the brain. It can kick off a process that converts protein to glucose. Peripheral cells in the body can start using more fat instead of glucose, conserving it for the brain.
“All these things, in addition to your stimulation of appetite, keep you going until you can get food,” Sue says. Should you go without food for a long time, use up all your fat and protein and become emaciated, she adds, you make ketone bodies, chemicals that can partially substitute for glucose.
It’s a system of symphonic grandeur. Ritter has helped chart it, locating glucose receptors in the primitive part of the hindbrain, charting their neural connections and chemical messengers, and linking them to parts of the brain that control feeding behaviors, hormone and neural responses designed to restore glucose levels.
Her questions are not far removed from those she asked as a doctoral student. But as her career developed, so did the tools, including a massive Rand McNally-like atlas.
“It’s how we find our way around in the brain,” she says, pulling it off a shelf.
Now, researchers can have antibodies deliver neuron-destroying toxins. These disable an animal’s feeding and help identify areas critical to the brain’s response to glucose deprivation. Genes responsible for the synthesis of neurotransmitters and other signaling elements can be localized, examined, silenced, deleted, and inserted.
The new technology has fortified the old, including the laboratory version of a deli slicer that can make mounted slides of tissue so thin they look like dried raindrops on a windshield. Special dyes in the samples help trace glucose-specific neurons. Under a microscope, they look like foam—dots and lines of cell bodies with wormlike axons and dendrites that can be charted through a chain of neurons.
But work at the brain’s cellular level quickly gets complicated. Branches from neurons influence many parts of the brain. Some neurons inhibit behavior; others excite it. Synapses can form and recede.
Such complexity extends into teasing out an animal’s feeding behavior.
“In the old days they thought, ‘Here’s a feeding center, here’s a satiety center, that’s all we need to know,’” Sue says. “‘You lesion the feeding center and the animal will stop eating, you lesion the satiety center, it can get fat.’ Now we know that there are systems in the brain that are totally interactive and important controls of food intake occur at different levels of the brain. So yeah, it’s not simple.”
We’re really laying into our plates now and things are getting wild, physiologically speaking.
We’re in a high-speed biological ritual of detecting, discriminating, and accepting. Our noses give our food stellar grades. A cranial nerve with a direct line from the tongue to the brainstem picks up texture and heat. Two other cranial nerves relay the sweetness that can cue us to food rich in calories, the savory meat taste known as umami, the saltiness of sodium needed to maintain blood volume and make nerves function. As the food passes the back of the mouth, the tongue checks for bitterness—a last-second security check for alkaloids and other poisonous stuff.
All systems are go. The menu is long, so we have no reason to stop. But as Bob Ritter knows, at some point we will. And it won’t necessarily be because we’re physically stuffed.
Even before food is absorbed, our gastrointestinal tract, from the mouth and stomach to the intestines, is gauging our food’s chemical and mechanical properties. The vagus nerve, wandering from the brainstem and throughout the gut, is a hotline of all-points bulletins.
With each swallow, the stomach relaxes a little bit in what’s called “receptive relaxation.” It keeps pressure from building up, lest it limit intake. Cut the vagus nerve, as when someone gets a vagotomy for a gastric ulcer, and the process goes away.
Empty a stomach as quickly as an animal eats and the animal will eat continuously.
But just down the line, the intestine appears to have a say in satiation as well.
“If we put nutrients into the intestine”—mimicking the satiation of normal eating—“we can stop the animal eating almost normally,” says Bob.
Our intestine may even, in effect, taste our food, he says. Cells embedded in the intestinal mucosa look a lot like those in the tongue. Some have the same taste-receptor molecules. When nutrients contact those cells, proteins similar to taste receptors release peptide hormones to the vagus nerve.
“There are some things that suggest that some of the proteins that allow us to taste food are involved in the detection of those same nutrients in the intestine,” says Ritter, “but it’s not something that we’re aware of in the same way.”
At last, we feel full. But as Ritter has seen, it is possible for people to say they’re full with nutrients in their intestine but an empty stomach.
The charming and intelligent Beth DeWeese poses another question: “Is it true that it takes 20 minutes for your brain to know your stomach is full?”
Early and powerful signals come while you’re eating, Bob reports, and the signals continue even after you’ve fully stopped. “But I don’t think anybody’s ever succeeded in experimentally showing that there’s a 20-minute lapse,” he says.
“The scientific basis for that is sound,” says Sue. “It takes a while to absorb the nutrients and get them into your circulation and for your hormones and so forth to begin to respond.”
Then there are those unfortunates who don’t seem to get the signals.
“One of the things that we’re really interested in is how, after you’ve been deprived of food for a long time, your stomach doesn’t get bigger,” Bob says. “It actually shrinks. And yet when you go back to eat, those cues that would turn off food intake tend to be more suppressed and you eat larger meals.”
It’s Oprah’s world: diet, then relapse.
“That’s the problem with every diet drug that’s been on the market,” says Sue. “As soon as you get off of it, you rebound. And it works the other way too. When you overeat and become obese, your intestinal length increases.” You accommodate more and get less full.
In a way, 100,000 years of feast and famine, not to mention millions of animal years, seem to have tailored the human body to follow two rules of eating now central to the Ritters’s professional lives: Miss glucose and die. Accumulate and store nutrients like fat and glycogen, maintaining a metabolic piggy bank for the lean times, and live.
“It’s an irony that in the 20th and 21st centuries we said obesity must be a disease,” says Bob. “But we both think the tendency to obesity may be something that’s adaptive in an evolutionary sense.”
A few years ago, Rick Rogers and his wife flew in their own airplane from Columbus, Ohio, to Pullman. Bob Ritter met them at the airport and they took him up for a ride. Twenty minutes or so later they were in Hell’s Canyon, the deepest river gorge on the continent, and Bob could see the Snake River meandering a mile below the rim and the Seven Devils Mountains thousands of feet above.
“I could see the tumblers going in his head,” Rogers says from Baton Rouge, where he’s a professor of neuroscience in the Louisiana State University system.
Soon after, the Ritters had their own plane and were flying to family and vacation spots throughout the Northwest and California.
“You’d never know it,” says Rogers, “but I think he’s adventurous as hell. She is too.”
That’s reflected in their work, adds Rogers, who has followed the Ritters for most of their careers.
“You have to be willing to take technical risks to advance your craft, and it’s risky, because if you’re wrong, you’re out of funding,” says Rogers. “You have to be willing to work the corners of the envelope, not unlike when you fly.”
In the 1940s and ’50s, neuroscientists grew to believe that both feeding and satiation were regulated by regions of the hypothalamus, just above the hindbrain, site of the medulla and pons. Working out of Pullman, away from better known neuroscience centers and looking at a less appreciated part of the brain, the Ritters were among the first to reveal important functions of the hindbrain in the control of food intake.
Sue, Rogers says, developed a greater understanding of how an animal’s physiological responses to low glucose are organized. By way of explaining how important this is, Rogers notes that “great handfuls” of your brain’s cortex can be removed, but you will survive. But damage your dorsal medulla, one of Sue Ritter’s main areas of focus, and you die. Immediately.
One possible implication of her work is a better understanding of a worst-case scenario of low glucose that is a complication of insulin therapy. If a diabetic takes too much insulin, it can lead to convulsions, coma, and death. The first times this happens, warning signs like shaking, sweating, and an urge to eat pop up. The fundamental problem is hypoglycemia, and eating makes the problem go away. But over time, repeated episodes of low blood sugar desensitize the body to the warning signs, hence the condition’s name: hypoglycemia unawareness.
Which brings us to another airplane story.
On a flight between Moscow and Boise, Idaho, the Ritters see a young man acting disoriented and irrational. He is starting to go into convulsions. Flight attendants ask him if he is on any special medications.
Sue Ritter, former flight attendant and working neuroscientist, is thinking, “hypoglycemia unawareness.” As it happens, the man is a diabetic whose schedule of eating and injections has been disrupted by travel. But at that particular moment, in the midst of his confusion, he manages to say just one word: “insulin.”
The flight attendants start making plans to give him insulin from his carry-on.
“It would have killed him,” says Sue. “We said, ‘Give him juice, give him sugar.’ He snapped right out of it. As soon as you give glucose, it’s like the parable of the Bible—take up your bed and walk. It’s just immediate.”
She’s referring to the story of Jesus healing a disabled man at the pool of Bethesda. Science is usually not so instant or miraculous. You follow your curiosity, slowly putting one foot in front of the other. And once in a while, thousands of feet up, you’re walking on air.
Brain’s role in eating—Sue and Bob Ritter’s work has identified areas of the brain and digestive system that stimulate appetite and signal satiation. (PDF)
Gallery: WSU appetite specialists Bob and Sue Ritter at the Black Cypress restaurant (Photos by Zach Mazur ’06)
Video: Gut Feelings: Decoding the Signals that Control Appetite
From the WSU Innovators video series
On the web
Brain maps (Wikipedia)
Gut Feelings: Decoding the Signals that Control Appetite (Presentation by Dr. Bob Ritter, WSU Innovators, April 23, 2008)