ALPHABETICAL BRAIN™ VOCABULARY
OF SECULAR SCIENCE STARS
August 31, 2021
The search for
what it means to be alive
by Carl Zimmer
(i-xx, 348 pages)
Quote = "Asking biologists about what it means for something to be alive makes for an awkward conversation. They will demur, stammer, or offer a flimsy notion that crumbles under even a little scrutiny. It is just not something that most biologists give much thought to in their day-to-day work. This reluctance has long mystified me, because the question of what it means to be alive has flowed through four centuries of scientific history like an underground river." (By the author of the book, Carl Zimmer, from the Introduction, page xix)
Quote = "Yet we feel our own life more strongly than we understand it. We know that other things are alive, too, like snakes and trees, even if we cannot ask them. Instead, we rely on the hallmarks that all living things seem to have. I took a tour of these hallmarks, getting to know creatures that display them in their most impressive, most extreme forms. Eventually my travels took me out to life’s edge, to the foggy borderland between the living and the nonliving, where I encountered peculiar things with some of life’s hallmarks but not others." (By the author of the book, Carl Zimmer, from the Introduction, page xix)
Quote = "Fascinating topics include assassin proteins, parthenogenesis, primate thanatology, and astrobiology. Five hallmarks of life are delineated: metabolism, homeostasis, information gathering, reproduction, and evolution. NASA has offered a definition, 'Life is a self-sustained chemical system capable of undergoing Darwinian evolution.'... Zimmer invites us to observe, ponder, and celebrate life's exquisite diversity, nuances, and ultimate unity." (From the Booklist Review book evaluation)
Quote = "We do not know when a theory of life might arrive, but we can hope, at least, that our own lives last long enough to let us see it... The newest explanation is called 'assembly theory'." (By the author of the book, Carl Zimmer, from Chapter 21, Four Blue Droplets, and slightly paraphrased by webmaster, page 288)
note = Numbers in parentheses refer to pages
INTRODUCTION --- The Borderland (ix-xx)
"When natural philosophers began contemplating a world made of matter in motion, they asked what set life apart from the rest of the universe. The question led scientists to many discoveries but also many blunders. Burke was hardly alone. For a brief time in the 1870s, for example, many scientists came to believe that the entire ocean floor was carpeted with a layer of throbbing protoplasm." (xix)
PART 1 --- THE QUICKENING (1-62)
"More than 150 years later, despite all that biologists have learned about living things, they still cannot agree on the definition of life. Puzzled, I set out on a trip. I started out in the heart of life’s territory: in the confidence that each of us has that we are alive, that we have a life that is bounded by birth on one side and by death on the other." (xix)
"Yet we feel our own life more strongly than we understand it. We know that other things are alive, too, like snakes and trees, even if we cannot ask them. Instead, we rely on the hallmarks that all living things seem to have. I took a tour of these hallmarks, getting to know creatures that display them in their most impressive, most extreme forms. Eventually my travels took me out to life’s edge, to the foggy borderland between the living and the nonliving, where I encountered peculiar things with some of life’s hallmarks but not others." (xix)
1) THE WAY THE SPIRIT COMES TO THE BONES (3-34)
note = See Excerpt at end of this outline for introductory information from this chapter.
2) DEATH IS RESISTED (35-62)
PART 2 --- THE HALLMARKS (63-125)
3) DINNER (65-77)
4) DECISIVE MATTER (78-89)
5) PRESERVING CONSTANT THE CONDITIONS OF LIFE (90-101)
6) COPY/PASTE (102-110)
7) DARWIN'S LUNG (111-124)
PART 3 --- A SERIES OF DARK QUESTIONS (125-200)
8) THIS ASTONISHING MULTIPLICATION (127-135)
9) IRRITATIONS (136-143)
10) THE SECT (144-151)
11) THIS MUD WAS ACTUALLY ALIVE (152-167)
12) A PLAY OF WATER (168-181)
13) SCRIPTS (182-200)
PART 4 --- RETURN TO THE BORDERLAND (201-292)
14) HALF LIFE (203-215)
19) DATA NEEDED FOR A BLUEPRINT (216-249)
20) NO OBVIOUS BUSHES (250-266)
21) FOUR BLUE DROPLETS (267-292)
"Someday humanity may draw a map that will make this journey easier. In a few centuries, people may look back at our understanding of life and wonder how we could have been so blinkered." (288)
"Life today is like the night sky four centuries ago. People gazed up at mysterious lights that wandered, streaked, and flared across the dark. Some astronomers at the time were getting the first inklings of why the lights traced their particular paths, but many of the explanations of the day would turn out to be wrong. Later generations would look up and instead see planets, comets, and red giant stars, all governed by the same laws of physics, all manifestations of the same underlying theory. We do not know when a theory of life might arrive, but we can hope, at least, that our own lives last long enough to let us see it... The newest explanation is called "assembly theory." (Paraphrased by webmaster from Chapter 21, Four Blue Droplets, page 288)
"You can think of the history of the universe as 13.7 billion years of things being put together. After the Big Bang, subatomic particles formed hydrogen atoms; helium atoms came about as hydrogen atoms joined together. Stars were assembled from hydrogen and helium, and in their stellar forges, new elements formed. Atoms assembled into molecules; molecules became grains. Planets and moons were built from them. On Earth snow flakes formed in the sky. Underground, minerals took shape. Once life emerged, it made things of its own. Organisms began making sugars, proteins, and cells. They grew tusks and flowers. Animals constructed beehives, beaver lodges, double-hulled canoes, and space probes. Cronin, Adamala, and Walker worked with colleagues on an objective way to compare how things get assembled, whether life is involved or not. The assembly of things happens in steps. A simple molecule may need just a single step to form from atoms. But it takes more steps to add extra atoms or to join two molecules together." (288)
"It is possible assembly theory has revealed a line cutting through life's borderland. Ordinary chemistry may not be able to assemble a material that needs 15 steps or more. Any one reaction may take place, given enough time. But the odds may be vanishingly small that a series of certain reactions happens in the right order --- and happens in that order again and again. Life, on the other hand, is a state of matter that can spontaneously make things with a lot of assembly steps... what allows life to do this is the special way in which information flows through it. In life, information is able to control matter. Genes and other molecular structures can store information, copy it into their offspring, and then channel that information through networks of proteins in order to do precise tasks --- such as making things in many steps of assembly." (289)
"Assembly theory might offer a way to look for life on other planets. It might he possible to detect life on planets orbiting other stars without even visiting them. Astronomers could use telescopes to scan the atmospheres of exoplanets for molecules. They detect a molecule with a high assembly number in abundance, they can be confident that it did not come into being through random chemistry. Only information could guide its production... Forget whether life is like a flame, forget whether it has a metabolism. Does the object have enough features to say that it cannot have formed randomly? And do you find it in abundance? If yes, then it is alive. If no, you cannot tell whether it was alive or not." [Suppositions and questions by scientist Cronin] (290)
ABOUT THE AUTHOR — Carl Zimmer (unpaged at end)
AUTHOR NOTES, SUMMARY
AND BOOK DESCRIPTION
AUTHOR NOTES = Carl Zimmer writes the Matter column for The New York Times and has frequently contributed to The Atlantic, National Geographic, Time, and Scientific American. He has won the American Association for the Advancement of Science's Science Journalism Award three times, among a host of other awards and fellowships. He teaches science writing at Yale, has been a guest on NPR's RadioLab, Science Friday, and Fresh Air, and maintains an international speaking schedule. He is the author of thirteen books about science, including She Has Her Mother's Laugh.
SUMMARY = We all assume we know what life is, but the more scientists learn about the living world — from protocells to brains, from zygotes to pandemic viruses --- the harder they find it is to locate life's edge. Zimmer leads us all the way into the labs and minds of researchers working on engineering life from the ground up. The book is an utterly fascinating investigation that no one but one of the most celebrated science writers of our generation could craft.
BOOK DESCRIPTION = Carl Zimmer investigates one of the biggest questions of all: What is life? The answer seems obvious until you try to answer it --- seriously! Is the apple sitting on your kitchen counter alive, or is only the apple tree it came from deserving of the word? If we cannot answer that question here on earth, how will we know when and if we discover alien life on other worlds? The question hangs over some of society's most charged conflicts. For example, is a fertilized egg a living person? And when should we declare a person legally dead?
Zimmer journeys through the strange experiments that have attempted to re-create life. Whether he is handling pythons in Alabama or searching for hibernating bats in the Adirondacks, Zimmer revels in astounding examples of life at its most bizarre. He tries his own experiment to evolve life in a test tube with unnerving results. He even charts the public's obsession with Dr. Frankenstein's monster and how Coleridge came to believe that the whole universe was alive.
Have scientists made life in the lab? Literally hundreds of definitions exist of what life should look like, but none has yet emerged as an obvious winner. Lists of what living things have in common do not add up to a theory of life. It is never clear why some items on the list are essential and others are not. Corona viruses have altered the course of history, and yet many scientists maintain they are not alive. And chemists are creating droplets that can swarm, sense their environment, and multiply.
EDITORIAL BOOK REVIEWS
PUBLISHER'S WEEKLY REVIEW = "The question of what it means to be alive has flowed through four centuries of scientific history like an underground river," writes journalist Zimmer (She Has Her Mother's Laugh) in this stimulating inquiry into biological fundamentals. He explores scientific phenomena that challenge simplistic concepts of what life and intelligence consist of (such as the notion that life is "something that sustained itself through chemical reactions"). Among his subjects are a girl who was declared brain-dead in 2013, but went on growing for years; hibernating bats whose metabolisms all but stop; and hypotheses about what creatures might lurk in the half-frozen sea of a moon of Saturn (namely, life that wouldn't need sunlight)."
"The author travels to laboratories, caves, and botanical gardens for colorful depictions of cutting-edge experiments, as with his reportage on a slime mold without neurons that 'followed the trail of sugar into the cul-de-sac and hit the acetate wall. But it did not give up its search. It sprouted tentacles to either side.' Zimmer discusses scientists' various definitions of life as well as different schools of thought, such as 'vitalists,' who believe life has a purpose, and 'mechanists,' who believe that life is 'made up of parts that work together, much like a clock.' The result is a pop science tour de force that extracts provocative insights from life's oddities." Agent: Eric Matthew Simonoff, WME.
BOOKLIST REVIEW = Our understanding of life is mostly intuitive, maybe prewired. Respected science writer Zimmer (A Planet of Viruses, 2011; She Has Her Mother's Laugh, 2018) diligently tackles the true definition of life. His curiosity and research lead him to a strange biologic limbo, "life's edge, to the foggy borderland between the living and the nonliving." Zimmer profiles creatures (rotifers, tardigraves, nematodes, multi-headed slime mold) capable of suspending their life, then, when conditions allow, "resurrecting" themselves. In the fabulous chapter, "Half Life," he considers the earth's biomes, providing clarity on Covid-19 and the viral populace at large. A mere spoonful of soil or liter of seawater holds a greater number of viruses than there are people on the planet. Zimmer suggests viruses "straddle" the boundary of living, while one scientist believes they have "a kind of borrowed life."
"Other fascinating topics include assassin proteins, parthenogenesis, primate thanatology, and astrobiology. Five hallmarks of life are delineated: metabolism, homeostasis, information gathering, reproduction, and evolution. NASA has offered a definition, "Life is a self-sustained chemical system capable of undergoing Darwinian evolution." Succinct, but hardly inspiring.The foremost question in biology --- What is life? --- remains strangely unanswered. For now, Zimmer invites us to observe, ponder, and celebrate life's exquisite diversity, nuances, and ultimate unity.
LIBRARY JOURNAL REVIEW = Journalist and author Zimmer (A Planet of Viruses) addresses the question of what it means to be alive; not so much in the philosophical sense, but by exploring the boundaries of the definition of "alive." Biologists have been refining the definitions of life through the centuries as they learn more about the diversity of living things. When does a new human life begin? What physiological signs mark the end of a life, beyond which there is no return? And, more broadly, what are the minimum essential characteristics something must possess to be considered a living thing: metabolism, response to stimulus, self-regulation, reproduction, ability to evolve? And is life a property of an organism, a species, or a single cell, or perhaps even smaller? From where did life emerge from non-living matter? If we were to look for life on another planet, how would we know we had found it? By profiling researchers working on these inquiries, Zimmer shows the complexity of reaching a single answer as each proposed definition has its edge cases that provide challenging counter-examples. VERDICT A fascinating and well-written mapping of the edges of biology, which will have broad appeal to nonscientists. – Wade Lee-Smith, University of Toledo Library.
AMAZON READER REVIEWS
 Wayne Lobb - Great book, a few minor comments = The celebrity endorsements are all true. Great book, a gripping read and an education, and exceptionally well-written. Some sentences and terminology did jar a bit: "Darwin hypothesized that a process he called natural selection would favor the variations that helped with surviving and having offspring." Darwin observed that animal breeders and plant growers cull --- artificially de-select --- organisms that have undesirable variations; so-called natural selection is just an (increasingly obsolete) shorthand for what goes on automatically in nature when some organisms happen to reproduce successfully while others do not. The quoted sentence is tautological.
Also: "Virus mutations may speed up the time it takes for the virus to replicate. They may enable a mutant virus to become invisible on the immune system’s radar. These viruses will be favored by natural selection." I suggest that it is better to say: These viruses will likely spread faster and farther than they would have otherwise. And finally: "Viruses can evolve resistance to antiviral drugs. They can evolve to adapt to a new host species." I know that viruses do not adapt in any active sense. Their replicates vary, always and unavoidably, due to imperfect copying of RNA/DNA and to mutations. Some variations might happen to enable the virus to replicate for the first time inside another host species. But my criticisms of the book are small matters. Great book!
 Bama Fan - Great book! Might be Zimmer's Best! I have read a few of Carl Zimmer's books including Parasite Rex, Microcosm, and A Planet of Viruses so I was excited to see what this book had in store. Zimmer explored some territory that people may remember in terms of origins of life as well as the connection between meteorites potentially bringing genetic material, but he also takes several twists and turns that are unexpected.
The book provides some recent data as well as some historical contexts for the origins of life and beliefs about those origins of life from a biological, chemical and, at times, philosophical perspective. At the beginning, each chapter seemed as if it was its own independent article and as the book progresses, Zimmer finds ways to weave some of these topics together while also highlighting work of scientists who do not get as much attention in other science books. The work of Albert Szent-Gyorgi and David Deamer were particularly interesting and insightful in their experiments and contributions to this and other topics. If you are someone like me who enjoys reading a lot about science, there is plenty of new ideas to consider and if you are someone who enjoys reading a good book without a science background, then you can navigate through this as easily as a liposome can navigate through your cells to deliver some RNA :)
 John L. Kubie - The book is divided into 4 sections. (useful to know when starting out):  Humans are "wired" to perceive life. Examples and studies of how we jump to conclusions;  Zimmer the naturalist takes us on a tour of remarkable specializations across living species. A remarkable set of living adaptations;  A historical tour of the concept of life, both dead ends and progress;  The evolution of living things. Ideas of how life started on our planet and how it might start on others. I was most interested in sections 3 and 4. Although I thought some things were missing, as usual with Carl I learned a lot, I found myself discussing and arguing with Carl (or particular scientists). Finally, I came away richer for the experience.
AMAZON READER REVIEWS
 Stories that both dazzle and edify… particularly brilliant in telling the story of DNA… Zimmer is an astute, engaging writer—inserting the atmospheric anecdote where applicable, drawing out a scientific story and bringing laboratory experiments to life. This book is not just about life, but about discovery itself. It is about error and hubris, but also about wonder and the reach of science. -- Siddhartha Mukherjee, New York Times Book Review.
 The pleasures of Life’s Edge derive from its willingness to sit with the ambiguities it introduces, instead of pretending to conclusively transform the senseless into the sensible. -- The Washington Post.
 A fascinating and well-written mapping of the edges of biology, which will have broad appeal to nonscientists. -- Library Journal (starred review).
 Diligently tackles the true definition of life... Zimmer invites us to observe, ponder, and celebrate life's exquisite diversity, nuances, and ultimate unity. -- Booklist (starred review).
 A master science writer explores the definition of life... An ingenious case that the answers to life's secrets are on the horizon. -- Kirkus Reviews.
 From the struggle to define when life begins and ends to the hunt for how life got started, the book, Life's Edge, offers an engaging, in-depth look at some of biology’s toughest questions. -- Science News.
 Carl Zimmer shows what a great suspense novel science can be. The book, Life's Edge, is a timely exploration in an age when modern Dr. Frankensteins are hard at work. But Carl’s artful, vivid, irresistible writing transcends the moment in these twisting chapters of intellectual revelation. Prepare to be enthralled. -- Jennifer Doudna, Nobel Laureate, co-author of the book, A Crack in Creation.
 Profound, lyrical, and fascinating, the book, Life’s Edge, will give you a newfound appreciation for life itself. It is the work of a master science writer at the height of his skills. It is a welcome gift at a time when life seems more precious than ever. -- Ed Yong, author of the book, I Contain Multitudes.
MORE PRAISE FOR CARL ZIMMER'S
OTHER SCIENCE BOOKS:
 One of the best science writers we have today. -- Rebecca Skloot, author of the book, The Immortal Life of Henrietta Lacks.
 No one unravels the mysteries of science as brilliantly and compellingly. -- David Grann, author of Killers of the Flower Moon.
 Nobody writes about science better. -- Neil Shubin, author of the books, Your Inner Fish and Some Assembly Required.
 Carl Zimmer makes the complex science of heredity read like a novel. -- Elizabeth Kolbert, author of the book, The Sixth Extinction.
SECTION 1 --- THE WAY THE SPIRIT COMES TO THE BONES (3-10)
As I made my way down a hairpin road, a sage-brush-studded wall of sand to my right, I felt keenly aware of my own life. I could feel the steep slope in my legs. After a series of tight turns, the wall swung away, revealing a long, desolate beach. It ran northward, a corridor of coast between high, slumping cliffs and the sea. Out over the Pacific, the sun hid behind clouds, a sky-wide bank of white. Earlier that day, in my hotel room, my phone had informed me the sky was cloudy and the temperature was in the low seventies. My brain responded to that information by choosing a light, long-sleeved shirt for my walk to the beach. And now my brain was updating its decision without cc'ing my conscious self.
Nerves sprinkled throughout my skin sensed the humidity and temperature of the layer of air encasing my body. Voltage spikes traveled from the nerve endings along long branches known as dendrites until they reached the cores of the nerves, called the somas. From there, new signals raced onward along long, cable-shaped extensions called axons. The axons reached my spine and traveled up toward my head. From neuron to neuron, the signals from the outside world made their way into my brain and finally to a nub of neurons deep inside my skull.
Those neurons combined the Morse code readout from across my body to generate new, different signals. They carried commands instead of sensations. The new voltage spikes left my brain along outward-bound axons, through my brain stem and down my spinal cord, until they reached millions of glands in my skin. There, they created electric charges in twisted tubes that wrung water out of the surrounding cells. Sweat ran down my back.
My conscious self was annoyed with the brain that generated it. One of the few shirts I had brought with me was now drenched in salt water.. I could not actually sense the trill of voltage spikes that shuttled information from skin to brain. I didn't feel a surge of blood in the center of my head as the heat-regulating part of my brain swung into action. In the moment, by the sea, I simply felt myself sweating. I felt annoyed. I felt alive.
As I felt aware of my own life, I also recognized other lives on the beach. A man walked lazily south, carrying a white-and-blue surfboard. Far to the north, a paraglider launched off from the top of the cliffs. The corkscrewing of the yellow paraglider wing spoke of intentions that arose in some human's brain and produced signals to hands gripping brake handles.
Along with human life, I could see feathered life as well. Sandpipers skittered along the surf. Their seed-sized brains sensed the flash of incoming waves and the cold foam around their legs, contracting muscles to keep their bodies upright, to scuttle to higher ground, to poke the sand for buried snails. The snails didn't quite have brains but rather fretworks of nerves that produced signals of their own for slowly, relentlessly burying their bodies into the earth. I contemplated the thousands of other subterranean nervous systems inside the mud dragons and the Pismo clams and other creatures buried below my feet. Out in the ocean, down the underwater canyon, other brains were swimming, carried along inside the buoyant bodies of leopard sharks and stingrays while the nerve nets of jellyfish drifted by.
After a few minutes of walking along the water, I stopped and looked down. A gigantic neuron, six feet long, lay on the sand. Most of it was made up of a glistening, caramel-colored axon. It curved gently like a heavily insulated electric cable. At one end it swelled into a bulb-shaped soma, which was crowned in turn by branches of dendrites. It could have been all that survived from a kraken that died in a battle with a pod of killer whales somewhere between here and Hawaii.
This fantastical neuron was, in fact, a stalk of elk kelp. It had washed up from an underwater forest a mile out to sea. What I had imagined to be an axon was the kelp's stipe, a trunk that not long ago anchored the organism to the ocean floor. What looked like a neuron's soma was in reality a gas-bloated bladder that kept the kelp upright in the ocean currents. The branching dendrites were the elk kelp's antlers, on which long blades had once grown. And the blades acted like the leaves of plants, catching what little sunlight filtered down through the seawater and fueling the growth of the elk kelps to heights that rivaled the palm trees that crowned the cliffs behind me.
The kelp had the kind of complexity that marks living things. But as I looked down at it, I could not say whether this particular kelp was still alive. I couldn't ask it how its day was going. It had no heartbeat I could check, no lungs to lift and lower a chest. But the kelp still glistened, its surfaces intact. Even if it could no longer capture sunlight, its cells might still be carrying on, using up its remaining fuel to repair its genes and membranes. At some point, maybe today or next week, its death would become certain.
But along the way, it would also become a part of life on land. Microbes would feast on its tough cuticles. Beach hoppers and kelp flies would follow, nibbling on its tender tissues. These wrack-feasting creatures would themselves become food for the sandpipers and terns. Plants would be fertilized by the kelp's nitrogen soaking into the ground. And a sweaty human being, his brain packed with thoughts of brains on this beach, would carry away in his neurons a memory of the kelp's neuron-like body.
The next morning I walked along the tops of the cliffs. North Torrey Pines Road cut north through La Jolla, California, alongside groves of looming tower cranes. With a stream of rush-hour traffic flowing by me, it was hard to remember the ribbon of wild coast tucked away close by. I crossed a eucalyptus-lined parking lot to get to the Sanford Consortium for Regenerative Medicine, a complex of glassed-in labs and offices. Once inside, I found my way to a third-floor laboratory, and there I met a scientist named Cleber Trujillo-Brazilian-born, with a close-cropped beard. Together we suited up in blue gloves and smocks.
Trujillo led me to a windowless room banked with refrigerators, incubators, and microscopes. He extended his blue hands to either side and nearly touched the walls. "This is where we spend half our day," he said.
In that room Trujillo and a team of graduate students raised a special kind of life. He opened an incubator and picked out a clear plastic box. Raising it above his head, he had me look up at it through its base. Inside the box were six circular wells, each the width of a cookie and filled with what looked like watered-down grape juice. In each well a hundred pale globes floated, each the size of a housefly head.
Every globe was made up of hundreds of thousands of human neurons. Each had developed from a single progenitor cell. Now these globes did many of the things that our own brains do. They took up the nutrients in the grape-juice-colored medium to generate fuel. They kept their molecules in good repair. They fired electrical signals in wavelike unison, keeping in sync by exchanging neurotransmitters. Each of the globes-which scientists call organoids-was a distinct living thing, its cells woven together into a collective.
"They like to stay close to each other," Trujillo said as he looked at the undersides of the wells. He sounded fond of his creations.
The lab where Trujillo worked was led by another scientist from Brazil named Alysson Muotri. After Muotri emigrated to the United States and became a professor at the University of California at San Diego, he learned how to grow neurons. He took bits of skin from people and gave them chemicals that transformed them into embryo-like cells. Dousing them with another set of chemicals, he steered tem to develp into full-blown neurons. They could form flat sheets covering the bottom of petri dishes, where they could crackle with voltage spikes and trade neurotransmitters.
Muotri realized that he could use these neurons to study brain disorders that arose from mutation. Instead of carving out a piece of gray matter from people's heads, he could take skin samples and reprogram them into neurons. For his first study, he grew neurons from people with a hereditary form of autism called Rett syndrome. Its symptoms include intellectual disability and the loss of motor control. Muotri's neurons spread their kelp-like branches across petri dishes and made contact with each other. He compared them to the neurons he grew from skin samples taken people without Rett syndrome. Some differences leaped out. Most noticeably, the Rett neurons grew fewer connections. It's possible that the key to Rett syndrome is a sparse neural network, which changes the way signals travel around the brain.
But Muotri knew very well that a flat sheet of neurons is a far cry from a brain. The three pounds of thinking matter in our heads are a kind of living cathedral, if a cathedral were built by its own stones. Brains arise from a few progenitor cells that crawl into what will become an embryo's head. They gather together to form a pocket-shaped mass and then multiply. As the mass grows, it extends long, cable-like growths out in all directions, toward the forming walls of the skull. Other cells emerge from the progenitor mass and climb up these cables. Different cells stop at different points along the way and begin growing outward. They become organized into a stack of layers, known as the cerebral cortex.
This outer rind of the human brain is where we carry out much of the thinking that makes us uniquely human-where we make sense of words, read inner lives on people's faces, draw on the past, and plan for the distant future. All the cells that we use for these thoughts arise in a particular three-dimensional space in our heads, awash in a complex sea of signals.
Fortunately for Muotri, scientists came up with new recipes to coax reprogrammed cells to multiply into miniature organs, known as organoids. They made lung organoids, liver organoids, heart organoids, and-in 2013-brain organoids. Researchers coaxed reprogrammed cells to become the rogenitor cells for brains. Provided with the right signals, those cells then multiplied into thousands of neurons. Muotri recognized that brain organoids would profoundly change his research.
A disease like Rett syndrome starts reworking the cerebral cortex from the earliest stages in the brain's development. For scientists like Muotri, those changes happened inside a black box. Now he could grow brain organoids in plain view. Together, Muotri and Trujillo followed the recipes that other scientists laid down for making organoids. Then they began creating recipes of their own to make a cerebral cortex. It was a struggle to find the blend of chemicals that could coax the brain cells onto the right developmental path. The cells often died along the way, tearing open and spilling out their molecular guts. Eventually the scientists found the correct balance. They discovered to their surprise that once the cells set off in the right direction, they took over their own development.
No longer did the researchers have to patiently coax the organoids to grow. The clumps of cells spontaneously pulled away from each other to form a hollow tube. They sprouted cables that branched out from the tube, and other cells traveled along the cables to form layers. The organoids even grew folds on their outer surface, an echo of our own wrinkled brains. Muotri and Trujillo could now make organoids that would grow to hundreds of thousands of cells. Their creations stayed alive for weeks, then months, then years.
"The most incredible thing is that they build themselves," Muotri told me.
On the day I visited Muotri's lab, he was checking in on some organoids he had sent into space. He sat in his office, a glass box perched out on a balcony next to the lab. Muotri had a gentle, relaxed manner, as if he might at any moment take off early from work, scoop up the scarred surfboard leaning against the wall by his desk, and head for the water. But today he was focused on the most extravagant of his many experiments. Outside his window, the paragliders were taking flight in the distance. He paid them no mind. Aboard the International Space Station, 250 miles above Muotri's head, hundreds of his brain organoids were sitting inside a metal box. He wanted to know how they were faring.
For years astronauts aboard the space station had run experiments to see how cells grow in low Earth orbit. As they free-fell around the planet, the cells no longer experienced the same tug of gravity that has pulled on all life on Earth for the past 4 billion years. Strange things happen in microgravity, it turned out. In some experiments, the cells grew faster than they would on the ground. They sometimes became bigger. Muotri was curious to see if his organoids would grow into larger clusters in space and perhaps become more like our own brains.
When they won approval from NASA, Muotri, Trujillo, and their colleagues began collaborating with engineers to build a home for organoids in space. They designed an incubator that could nurture the organoids, keeping the conditions right for their development. A few weeks before I visited the lab, Muotri had poured a fresh batch of miniature brains into a vial, which he put in a backpack. Standing in the security line at San Diego International Airport, he had no idea what he'd say if anyone asked what was in the tube. These are a thousand miniature brains I have grown in my lab, and I am about to put them into space.
Apparently, organoids do not grab that kind of attention. Muotri managed to board his flight without getting questioned. When he got to Florida, he handed the tube over to the engineers for a flight aboard a supply rocket. A few days later Muotri watched the SpaceX Falcon 9 rise from the earth.
When the payload arrived at the space station, the astronauts grabbed the box loaded with organoids and plugged it into a bay. There it sat for a month. When the experiment was over, the astronauts would dunk the organoids in alcohol. They would die, but their life would be frozen at the moment of death. Once they fell back into the Pacific, were fished out, and were delivered to Muotri's lab, he would be able to inspect their cells and see which genes they had used in space. (3-10)
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