To Unlock the Brain’s Mysteries, Purée It Keep supporting indian students
By Ferris Jabr
One day in June 2012, at São Paulo’s international airport, Suzana Herculano-Houzel hauled two heavy suitcases onto an X-ray-machine conveyor belt. As the luggage passed through the scanner, the customs agent’s eyes widened. The suitcases did not contain clothes, toiletries or any of the usual accouterments of travel. Instead, they were stuffed with more than two dozen curiously wrapped bundles, each enclosing an amorphous blob suspended in liquid. The agent asked Herculano-Houzel to open her bags, suspecting that she was trying to smuggle fresh cheese into the country; two people had been caught doing exactly that just moments before.
“It’s not cheese,” Herculano-Houzel said. “It’s only brains.”
She was a neuroscientist, she explained, and she had just returned from an unusual — but completely legal — research expedition in South Africa, where she collected brains from a variety of species: giraffes, lions, antelopes, mongooses, hyenas, wildebeests and desert rats. She was taking the organs, sealed in containers of antifreeze, back to her lab in Rio de Janeiro. The customs agents reviewed her extensive collection of permits and documentation, and they eventually let her pass with suitcases in tow.
A brain is a precious thing, containing many of science’s greatest unsolved mysteries. What we don’t know about the brain still eclipses what we do. We don’t know how the brain generates consciousness. We aren’t sure why we sleep and dream. The precise causes of many common mental illnesses and neurological disorders elude us. What is the physical form of a memory? We have only inklings. We still haven’t cracked the neural code: that is, how networks of neurons use electrical and chemical signals to store and transmit information. Until very recently — until Herculano-Houzel published an important discovery in 2009 — we did not even know how many cells the human brain contained. We only thought we did.
Before Herculano-Houzel’s breakthrough, there was a dominant narrative about the human brain, repeated by scientists, textbooks and journalists. It went like this: Big brains are better than small brains because they have more neurons, and what is even more important than size is the brain-to-body ratio. The most intelligent animals have exceptionally large brains for their body size. Humans have a brain seven times bigger than you would expect given our overall size — an unrivaled ratio. So, the narrative goes, something must have happened in the course of human evolution to set the human brain apart, to swell its proportions far beyond what is typical for other animals, even for our clever great-ape and primate cousins. As a result, we became the bobbleheads of the animal kingdom, with craniums spacious enough to accommodate trillions of brain cells: 100 billion electrically active neurons and 10 to 50 times as many supporting cells, known as glia.
By comparing brain anatomy across a large number of species, Herculano-Houzel has revealed that this narrative is seriously flawed. Not only has she upended numerous assumptions and myths about the brain and rewritten some of the most fundamental rules about how brains are constructed — she has also proposed one of the most cohesive and evidence-based frameworks for human brain evolution to date.
But her primary methods are quite different from others’ in her field. She doesn’t subject living brains to arrays of electrodes and scanners. She doesn’t divide brains into prosciutto-thin slices and carefully sandwich them between glass slides. She doesn’t seal brains in jars of formaldehyde for long-term storage. Instead, she demolishes them. Each organ she took such great care to protect on her trans-Atlantic journey was destined to be liquefied into a cloudy concoction she affectionately calls “brain soup” — the key to her groundbreaking technique for understanding what is arguably the most complex congregation of matter in the universe. In dismantling the brain, she has remade it.
For decades, the standard method for counting brain cells was stereology: slicing up the brain, tallying cells in thin sheets of tissue splayed on microscope slides and multiplying those numbers by the volume of the relevant region to get an estimate. Stereology is a laborious technique that works well for small, relatively uniform areas of the brain. But many species have brains that are simply too big, convoluted and multitudinous to yield to stereology. Using stereology to take a census of the human brain would require a daunting amount of time, resources and unerring precision.
“I realized we didn’t know the first thing about what the human brain is made of, much less what other brains were made of, and how we compared”
In a study from the 1970s, Herculano-Houzel discovered a curious proposal for an alternative to stereology: Why not measure the total amount of DNA in a brain and divide by the average amount of DNA per cell? The problem with this method is that neurons are genetically diverse, the genome is a highly dynamic structure — continuously unraveling and reknitting itself to amplify or silence certain genes — and even small errors in measuring quantities of DNA could throw off the whole calculation. But it gave Herculano-Houzel a better idea: “Dissolve the brain, yes! But don’t count DNA. Count nuclei!” — the protein-rich envelopes that enclose every cell’s genome. Each cell has exactly one nucleus. “A nucleus is a nucleus, and you can see it,” she says. “There is no ambiguity there.”
She began experimenting with rat brains, freezing them in liquid nitrogen, then puréeing them with an immersion blender; her initial attempts sent chunks of crystallized neural tissue flying all around the lab. Next she tried pickling rodent brains in formaldehyde, which forms chemical bridges between proteins, strengthening the membranes of the nuclei. After cutting the toughened brains into little pieces, she mashed them up with an industrial-strength soap in a glass mortar and pestle. The process dissolved all biological matter except the nuclei, reducing a brain to several vials of free-floating nuclei suspended in liquid the color of unfiltered apple juice.
To distinguish between neurons and glia, Herculano-Houzel injected the vials with a chemical dye that would make all nuclei fluoresce blue under ultraviolet light, and then with another dye to make the nuclei of neurons glow red. After vigorously shaking each vial to evenly disperse the nuclei, she placed a droplet of brain soup on a microscope slide. When she peered through the eyepiece, the globular nuclei looked like Hubble photos of distant stars in the black velvet of space. Counting the number of neurons and glia in several samples from each vial, and multiplying by the total volume of liquid, gave Herculano-Houzel her final tallies. By reducing a brain, in all its daunting intricacy, to a homogeneous fluid, she was able to achieve something unprecedented. In less than a day, she accurately determined the total number of cells in an adult rat’s brain: 200 million neurons and 130 million glia.
Rat brains were just the beginning. “Once I realized I could actually do this,” Herculano-Houzel told me, “there was a whole world of questions out there just waiting to be examined.” Which is to say, there was a whole planet of brains waiting to be dissolved.
By 2016, Herculano-Houzel had migrated to Vanderbilt University. She has published studies on the brains of more than 80 species. The more species she has compared, the clearer it has become that much of the dogma about brains and their cellular components is simply wrong. First of all, a large brain does not necessarily have more neurons than a small one. She has found that some species have especially dense brains, packing more cells into the same volume of brain tissue as their spongier counterparts. As a rule, because their neurons are smaller on average, primate brains are much denser than other mammalian brains. Although rhesus monkeys have brains only slightly larger than those of capybaras, the planet’s largest rodents, the rhesus monkey has more than six times the number of neurons.
The brain-soup technique further revealed that the human brain, contrary to the numbers frequently cited in textbooks and research papers, has 86 billion neurons and roughly the same number of glia — not 100 billion neurons and trillions of glia. And humans certainly do not have the most neurons: The African elephant has about three times as many. When Herculano-Houzel focused on the cerebral cortex, however — the brain’s wrinkled outermost layer — she discovered a staggering discrepancy. Humans have 16 billion cortical neurons. The next runners-up, orangutans and gorillas, have nine billion; chimpanzees have six billion. Humans seemed to possess the most cortical neurons — by far — of any species on earth.
A cross-section of a preserved human brain looks like a slice of gnarled squash, with an undulating cream-colored interior outlined by an intensely puckered gray rind. That rind — composed of layers of densely packed neurons and glia — is the cerebral cortex. Its deep grooves and ridges significantly increase its total surface area, providing more room for cells within the confines of the skull. All mammals have a cortex, but the extent to which the cortex is wrinkled depends on the species. Squirrels and rats have cortices as smooth as soft-serve, whereas human and dolphin brains look like heaps of udon noodles. Over the years, some researchers have proposed that the more corrugated the cortex, the more cells it contains, and the more intelligent the species. But no one had precise cell counts to back up those claims.
Were there a bird with a brain the size of a grapefruit, however, it would probably rule the world.
The cerebral cortex is the difference between impulse and insight, between reflex and reflection. It is essential for voluntary muscle control, sensory perceptions, abstract thinking, memory and language. Perhaps most profound, the cerebral cortex allows us to create and inhabit a simulation of the world as it is, was and might be; an inner theater that we can alter at will. “The cortex receives a copy of everything else that happens in the brain,” Herculano-Houzel says. “And this copy, while technically unnecessary, adds immense complexity and flexibility to our cognition. You can combine and compare information. You can start to find patterns and make predictions. The cortex liberates you from the present. It gives you the ability to look at yourself and think: This is what I am doing, but I could be doing something different.”
The sheer density of the human cortex dovetails with an emerging understanding of interspecies intelligence: It’s not that the human mind is fundamentally distinct from the minds of other primates and mammals, but rather that it is dialed up to 11. It’s a matter of scale, not substance. Many mental abilities once regarded as uniquely human — toolmaking, problem-solving, sophisticated communication, self-awareness — turn out to be far more widespread among animals than previously thought. Humans just manifest these talents to an unparalleled degree. Herculano-Houzel thinks the simplest explanation for this disparity is the fact that humans have nearly twice as many cortical neurons as any other species studied so far. How, then, did our species gain such a huge lead?
The standard explanation for our unrivaled intelligence is that humans bucked the evolutionary trends that restricted other animals. Somehow, perhaps because of a serendipitous genetic mutation millions of years ago, the human brain inflated far beyond the norm for a primate of our body size. But Herculano-Houzel’s careful measurements of dozens of primate species demonstrated that the human brain is not out of sync with the rest of primatekind. In both mass and number of cells, the brains of all primates, including humans, scale in a neat line from smallest to biggest species — with the exception of gorillas, orangutans and chimpanzees. The great apes, our closest evolutionary cousins, are the anomalies, with oddly shrunken brains considering their overall heft. While contemplating this incongruity, Herculano-Houzel remembered a book she read a few years earlier: “Catching Fire: How Cooking Made Us Human,” by the Harvard anthropologist Richard Wrangham.
Wrangham proposed that the mastery of fire profoundly altered the course of human evolution, to the extent that humans are “adapted to eating cooked food in the same essential way as cows are adapted to eating grass, or fleas to sucking blood.” Cooking neutralized toxic plant compounds, broke down proteins in meat and made all foods much easier to chew and digest, meaning we got many more calories from cooked foods than from their raw equivalents. Because our digestive systems no longer had to work as hard, they began to shrink; in parallel, our brains grew, nourished by all those extra calories. The human brain makes up only 2 percent of our body weight, yet it demands 20 percent of the energy we consume each day.
Herculano-Houzel realized that she could extend and modify this line of thought. In the wild, modern great apes spend about eight hours a day foraging just to meet their minimal caloric requirements, and they routinely lose weight when food is scarce. In the course of their evolutionary history, as they developed much larger bodies than their primate ancestors, with larger organs to match, their brains most likely hit a metabolic growth limit. Great apes could no longer obtain enough calories from raw plants to nourish brains that would be in proportion with their overall mass.
Cooking liberated our ancestors from this same physiological straitjacket and put us back on track to develop brains as large as expected for primates our size. And because primates have such dense brains, all that new brain mass rapidly added a huge number of neurons. It took 50 million years for primates as a group to evolve brains with around 30 billion neurons total. But in a mere 1.5 million years of evolution, the human brain gained an astounding 56 billion additional neurons. To use the metaphor of our time, cooking tripled the human brain’s processing power.
Ultimately, the brain-soup technique’s central strength — its reductionism — is also its weakness. By transforming a biological entity of unfathomable complexity into a small set of numbers, it enables science that was not previously possible; at the same time, it creates the temptation to exalt those numbers. In her book, “The Human Advantage,” Herculano-Houzel stresses the distinction between cognitive capacity and ability. We have about the same number of neurons as humans who lived 200,000 years ago, yet our respective abilities are vastly different. At least half of human intelligence derives not from biology but from culture — from the language, rituals and technology into which we are born.
For centuries, we have regarded the brain as a kind of machine: a ludicrously convoluted one, but a machine nonetheless. If we could only pick it apart, quantify and examine all its components, we could finally explain it. But even if we could count and classify every cell, molecule and atom, we would still lack a satisfying explanation of its remarkable behavior. The brain is more than a thing; it’s a system. So much of intelligence is neither within the brain nor in its environment, but vibrating through the space in between.