Brainiac: With her innovative ‘brain soup,’ Suzana Herculano-Houzel is changing neuroscience one species at a time

By Michael Blanding
FEDERICA BORDONI

FEDERICA BORDONI

 

Some myths never seem to die. Take the canard that humans use only 10 percent of their brains, leaving vast reservoirs of gray matter untapped. That myth goes back at least as far as Dale Carnegie’s 1936 book, How to Win Friends and Influence People, and has cropped up as recently as the 2014 Scarlett Johansson movie Lucy.

The persistence of that myth proved so galling to Suzana Herculano-Houzel, Vanderbilt associate professor of psychology and biological sciences, that when she worked as a science educator at the Museu da Vida in Rio de Janeiro, she conducted a survey in 2002 and found that 60 percent of the college-educated public believed it. “Which is completely wrong! We use 100 percent of the brain, 100 percent of the time,” Herculano-Houzel says. “It’s one of those pieces of popular culture that just keeps going around.”

A neuroscientist with a master’s degree from Case Western Reserve University and a doctorate from Universite Pierre et Marie Curie in Paris, Herculano-Houzel figured the first step to disproving the myth was to determine exactly how many neurons the brain actually contains. Consequently, she began searching through the scientific literature for an answer.

The more she looked, however, the more myths she found.

Scientists routinely bandied about the number 100 billion, but that seemed based on an order-of-magnitude estimate extrapolated from only parts of the brain. “We really didn’t know the first thing about the actual number,” Herculano-Houzel says. “It was a bunch of intuitions people heard about second- or thirdhand. Everyone thought everyone else already knew, so nobody bothered anymore.”

Her search for the answer to a seemingly simple question ultimately steered Herculano-Houzel back into academia and soon led her to develop a new method to measure the number of neurons in the brain. The resulting number for humans turned out to be 86 billion. To a nonscientist that may seem like a small distinction, but as Herculano-Houzel points out, “The difference is an entire baboon brain and change.” Since first pioneering the new technique, she has applied it to dozens of animal species, introducing a whole new frontier in evolutionary neuroscience.

Herculano-Houzel summarized her findings last year in a book, The Human Advantage: A New Understanding of How Our Brain Became Remarkable (MIT Press), around the same time she joined the psychological sciences department at Vanderbilt.

“There is a lot of data on brain size, but if you don’t know the number of neurons, you are limited in what you can theorize about,” says Jon Kaas, Gertrude Conaway Vanderbilt Distinguished Professor of Psychology. What sets Herculano-Houzel apart, Kaas says, is not just the data she’s uncovered, but how she has analyzed it to discover previously unknown truths about our most powerful organ. “She is absolutely innovative in thinking about what these results mean.”

QUEST FOR THE TRUTH

Herculano-Houzel talks with an easygoing humor and an infectious love of science. “I was born an optimist, to the point that it annoys people,” she laughs. She was raised in Rio by academic parents, her mother a sociologist and her father an economist. Despite the chronic lack of funding for science in Brazil, her parents encouraged her to follow her passion for biology. “It was a terrible idea because there was no market for it,” she says.

Her positivity paid off when she left Brazil for Case Western in Cleveland, originally intending to study molecular genetics. “My undergrad curriculum didn’t include anything about brains. I went to grad school not knowing we had brains,” she jokes. When a classmate encouraged her to look into neuroscience, she was immediately hooked by the diversity of the field.

“Neuroscience is really about all aspects of life,” Herculano-Houzel says. “You step outside the lab, and it’s not over; it’s all about how you get by and how you know things.”

Faced with increasing specialization after earning her doctorate at Pierre et Marie Curie, Herculano-Houzel decided to return to Brazil and broaden her studies even more by becoming a science educator, finding work at the Museu da Vida—Portuguese for “Museum of Life.” There she discovered a flair for breaking down complex scientific truths into everyday language. Soon she was writing a science blog on the side, interpreting the latest findings in neuroscience for general audiences.

“I realized people were interested in hearing that there is actually a reasonable answer to why you forget where you put the parking ticket, or why if you lose your train of thought, you need to go back to the room where you lost it to find it again.”

From the beginning, she set out to make science fun. But underneath was a deeper motivation—frustration at the short shrift science was often given in her home country. “People had no understanding of what science was actually about,” she says. “I figured that by making it accessible and fun, they would push the government to support more of it.”

That desire led to her quest of seeking out the truth behind how many neurons were actually in the brain. In the past neuroscientists had tried to answer that question by slicing the brain into thin sections, then counting the neurons in samples of representative slices. Because different brain parts have different densities of neurons, the technique couldn’t determine the number in the entire brain accurately.

ALL PHOTOS COURTESY OF SUZANA HERCULANO-HOUZEL

 

BRAIN SOUP

Herculano-Houzel stumbled across papers from the 1970s, however, that described attempts by scientists to dissolve brains into a liquid soup to measure the concentration of DNA. She surmised the method could be adapted to liquefy the cell membranes while leaving the nuclei intact. By counting the remaining nuclei in a small sample, a researcher could then multiply it by the overall volume to determine the total number of neurons.

Dissolving brain cells turned out to be remarkably easy: All you needed was a detergent that could dissolve fatty membranes while leaving the protein-rich nuclear membranes intact. “It is really just like a kitchen detergent,” says Herculano-Houzel. When she tried it, however, she found that the proteins in the nuclei weren’t tightly bound enough to prevent them from dissolving as well. She tried flash-freezing the brains in liquid nitrogen, then throwing them in a blender. But that only made them crack. “I had pieces of brain all over the lab,” she recalls.

Finally, she tried fixing the brain tissue first with formaldehyde before dissolving it. “That turned out to be the trick to keep the nuclei perfectly stable,” she says. The result was a grainy soup that looks like unfiltered apple juice, where nuclei are easily counted. “My students say I have totally killed apple juice for them,” she says. From there she could apply a fluorescent stain to differentiate the neurons from the other cells in the brain to get an accurate count.

Herculano-Houzel started using the technique on rat brains before moving up to larger rodents—all the way to the capybara, a South American rodent that is the largest in the world. She found as the animals got larger, they had more neurons, but at densities that decreased proportionately. Her work caught the interest of Kaas, who saw her present findings at a conference, and he invited her to Vanderbilt in January 2006 to test her technique on primate brains. Although they had only three species, they found a clear pattern. Not only did the primates have many more neurons than the rodents, but they also maintained the same neuron density as they increased in size—meaning the larger they got, the more computing power per gram they had.

When she finally applied the technique to the human brain, Herculano-Houzel discovered we have an average of 86 billion neurons. Surprisingly, though, the neuron density is the same as in other primates, showing a clear evolutionary pattern from monkeys to humans. “We somehow manage to have this large brain with a large number of neurons; but it’s still just a regular primate brain,” says Herculano-Houzel.

What makes humans unique is the sheer number of neurons in the brain—especially in the cerebral cortex, the part of the brain that controls higher cognitive functions. “The cerebral cortex sits on top of the brain and gets a copy of all the information being processed and has the opportunity to add to it,” Herculano-Houzel explains. “The more neurons you have in the cerebral cortex, the more complex your behavior can be.”

After their experiments together, Kaas began introducing Herculano-Houzel more widely in the field, opening doors for her with other researchers. “I was a nobody, an outsider,” says Herculano-Houzel. “Jon endorsed what I was doing, and pushed me to publish.” When she did publish her paper detailing the number of neurons in the human brain in 2009, it became a sensation, quickly becoming one of the most widely cited papers in neuroscience.

She continued to travel to Vanderbilt at least once a year to give lectures that were always well-attended—because of the significance of her findings, as well as the clarity with which Herculano-Houzel expressed them—and began collaborating with researchers around the world.

“Her energy is amazing,” Kaas says. “She collaborates with 30 or 40 people around the world, and I’ve never heard anyone say they did more work than she did.”

JORGE BISPO

JORGE BISPO

 

COOKING CHANGED EVERYTHING

Among her recent findings is a new explanation for the number of folds in the brain, a question that has vexed the field for years. Other neuroscientists have posited explanations from genetics to lifestyle to explain them. Working with a physicist, Herculano-Houzel determined the number could be reduced to a simple formula based on the size and thickness of the cortex on the exterior of the brain. “It was such a simple solution,” Kaas says, “but it took figuring out a way to generate the data.”

Herculano-Houzel also has continued to apply her brain-soup techniques to an ever-increasing number of species, determining the true geniuses of the animal kingdom. Kelly Lambert, a professor of behavioral neuroscience at the University of Richmond, first reached out to Herculano-Houzel when she was writing a textbook on the brain, but quickly implored her to collaborate on her own research on raccoons, which are known for their unique problem-solving abilities. “The very reason many people hate them for getting into their garbage cans is why I love them,” says Lambert.

Their results showed that neuron density is much higher in raccoons than in other rodents, and that a raccoon’s brain resembles that of a small primate. Applying the techniques to different species can confirm our suspicions about the intelligence of some species, as well as offer new insights into the brains of animals that excel in certain areas that may outstrip humans, such as raccoons’ hand dexterity or dogs’ sense of smell. “She is changing the way we think about brains on a rudimentary level,” Lambert says.

Nowhere is Herculano-Houzel changing our understanding of the brain more, however, than for our own species. In her recent book, The Human Advantage, she builds on her theories about human brain evolution by comparing humans to bigger primates. Although gorillas and orangutans are two to three times our size, they have smaller brains than humans, which is why scientists have believed the human brain is bigger than it should be for our body size.

Herculano-Houzel theorizes that the discrepancy comes down to a simple question of energy: These animals can’t take in enough calories in a day to support both a large body and a powerful brain, so evolution ended up favoring a larger body. On the face of it, however, the same problem should beset humans, whose brains consume 25 percent of the calories the body takes in. In the wild, she calculates, humans would have to spend more than nine hours a day eating just to consume enough calories to support both their bodies and brains.

Herculano-Houzel attributes the fact that we don’t spend so much time foraging to a uniquely human act: cooking. By using stone tools, then learning to use fire, in order to transform food into a more palatable form, we dramatically increased the number of calories, bite for bite, that we retain from food. “Raw foods take a long time to chew,” Herculano-Houzel says. Even after we have chewed and swallowed a carrot, we still haven’t completely turned it into a puree. “So you only assimilate 40 percent of the calories,” says Herculano-Houzel. “But if you cook the same carrot, then it will be completely broken down and assimilated.”

Her findings provide the data to support other theories about the importance of cooking put forward by evolutionary biologists. “I had demonstrated the importance of cooking by showing it reduced the amount of time in chewing,” says Richard Wrangham, professor of biological anthropology at Harvard, “but I hadn’t put that together with the notion that if we were eating our food raw, we simply wouldn’t have enough time to take in all the fuel our brains need.”

At Vanderbilt, Herculano-Houzel will continue her research into brain neuronal density, examining different parts of the human brain to determine not only what it has to tell us about cognition, but also about metabolism, sleep, longevity and other functions. As she unlocks more information about the brain, she hopes to explain more about what distinguishes us from other species, and makes us human.

“It’s been really rewarding to be able to provide data for these parts of the story that were previously based on intuition,” she says, “and quite humbling to understand how we humans fit into it.”


Michael Blanding is a Boston-based author and investigative journalist whose work has appeared in Wired, SlateThe NationConsumers DigestThe Boston Globe Magazine and Boston Magazine. His latest book, The Map Thief (2014, Gotham Books), was named a New York Times best-seller and an NPR Book of the Year.


Read Suzana Herculano-Houzel’s groundbreaking paper that became a sensation among neuroscientists worldwide in 2009.



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