Promotion
Free shipping on $45+ Shop Now!
Decoding the World
A Roadmap for the Questioner
Contributors
By Po Bronson
By Arvind Gupta
Formats and Prices
Price
$11.99Price
$15.99 CADFormat
Format:
This item is a preorder. Your payment method will be charged immediately, and the product is expected to ship on or around October 6, 2020. This date is subject to change due to shipping delays beyond our control.
Also available from:
Excerpt
About the Cover Art
The cover image and design, by Jarrod Taylor, is inspired by the Dutch surrealist graphic artist M. C. Escher, whose works Bond of Union and Rind were, in turn, inspired by H. G. Wells’s novel The Invisible Man.
The genetic code inside the ribbon—the bases of As, Ts, Cs, and Gs—is not random. Here is the full code:
CTCTGTTAGCGTCTGCTCGTCAGCCTGTGAAGCCTGCTCCTAGTACTGTAGACTCATATCCTA
Using a simplified grade-school DNA writer, this can be decoded into plain text:
NOTHING IS INEVITABLE
About This Book
Decoding the World, at its core, tells the story of a friendship. It’s a buddy story. It starts with Po coming to IndieBio—and ends two years later with Arvind leaving IndieBio.
Arvind created IndieBio as a laboratory for early biotech startups trying to solve major world problems. Glaciers melting. Dying bees. Infertility. Cancer. Ocean plastic. Pandemics.
There are some truths you can only learn through doing. And there are other truths you can only access by slowing down and really synthesizing. Arvind and Po embody this duality. Arvind is the fearless one, a radical experimentalist. Po is like the detective, patiently looking for clues others have missed. When they meet, their styles mix and create a quadratic speedup of creativity. Yin and yang crystallized.
The villain they’re fighting is inertia. The status quo. They find scientists to create companies to solve important world problems. But it’s hard. Capitalism fights back. One might say they are up against Isaac Newton’s First Law of Motion, which says the bigger the mess, the easier it is to just keep going the same way we’ve always done it.
Unexpectedly, over the course of the two years, a classic Hollywood role reversal transforms them both. Arvind learns to think slower to build bigger. Po learns to act faster to see further.
As Arvind’s departure draws near, he struggles to leave the sanctum he created. While Po has to prove he can keep the “indie” in IndieBio after Arvind is gone.
1
First Coronavirus Death in U.S. and New Cases Detected as Testing Expands Washington Post
Craig needed three days to start testing.
Akash wanted to start a clinical trial in 10 days.
Melanie needed 32 days to grow antibodies and sequence them.
Franco needed 45 days for his CRISPR test, which would drop the cost of testing to five dollars.
First went the handshakes. Second went travel. Everyone canceled their trips.
Even in a crisis, people want to look smart and rational. There was a compulsion across society to use the little we knew to declare predictions. It took several weeks to recognize the futility of looking into the future. The only honest people were those who admitted, this is the unknown.
There was no plan, just a way. We all went home from IndieBio, vacating the lab so Franco’s team from Argentina could take it over and develop their test. After a day, we couldn’t stand the feeling of retreat. This was not us. Our philosophy is action.
Then Arvind got the email from Akash.
Akash had a proposal to stop COVID-19. I forwarded it to the team.
Text from my sister, who is an eye surgeon at a major hospital in New York:
Sad case today. A 17-year-old with a bad injury from yard work. Full corneal laceration, traumatic cataract and retinal detachment. His father was so devastated. When we were talking he collapsed and hugged me out of sorrow. Now I feel like I’m covered in corona.
Akash wrote that he had 735 kilograms of niclosamide on its way to the U.S. They were going to use it for a clinical trial as a form of birth control, as a spermicide. But they wanted to try it for COVID-19. They were in contact with the FDA. Niclosamide was invented by Bayer in the 1950s and was mostly used in the developing world to treat tapeworm. It had been pulled off the U.S. market in 1996, but it was still made elsewhere.
The argument was that niclosamide might work because, even though it had never been used to treat SARS or MERS during an outbreak, long after the fact it was shown that niclosamide could stop those viruses from replicating inside us. The COVID-19 virus had the same 11 proteins as SARS and MERS, the same arsenal of weapons.
Normally, VCs take weeks or months to study a deal. This took us about an hour to say yes, which was the length of our first phone call. It was a blind bet with no evidence, only theory. Usually those bets bust. We would have been fine with that.
We were worried about Craig. He’d been coming by the lab to borrow our RT-PCR for weeks. He was so frustrated by the lack of testing that he invented an alternative to the CDC’s protocol. He took four steps and simplified it into one step. He and Gabe were out on the street, testing random people, including the homeless.
Then Craig got some positive samples from UCSF, and he was able to confirm his test worked. He had a lab space arranged. He could start testing in three days, but he needed money to buy a real-time ABI7500DX PCR to handle the volume. When we tried to wire him $250,000, he realized he hadn’t even set up a bank account yet.
Sleep was important. Sleep as much as possible. Roll out of bed, Zoom calls for fourteen hours. Days became a photocopy of the day before. Without the texture of moving around the city, or bouncing around IndieBio, I became forgetful; my memories were unmoored from geography, synthetic, like boring dreams I couldn’t wake from.
Arvind wrote a letter to all our alumni:
“Nobody knows how long this will last. Nobody knows how this will end. I do know this. Nothing is ever as good as it looks or as bad as it feels. We will be fine. We may even be better from it. But first, we must survive it. You are all IndieBio companies. Which means you are already survivors. Born and bred in the basement on Jessie Street in the Tenderloin. Walking into the office meant stepping over the hardships of life just to face it again in the lab. But this shock is different. Covid-19 will test us all.”
At least a dozen of our alumni were running into the fire.
In Korea, their Zoonotic Virus Lab tried 3,000 existing drugs, in a high-throughput screen using kidney cells infected with the virus. They found 24 that worked well, and niclosamide was one of the two that stood out above the rest. We called the Gates Foundation to get it on their radar. Around the same time, Akash got great results back on niclosamide from the Galveston National Lab, a Biosafety Level 4 containment facility that worked with live virus. Three medical centers had agreed to start a trial.
Text from my sister in New York:
I have an emergency transplant to do. She will lose her eye by tomorrow. Patient should be tested for COVID but hasn’t. The virus becomes airborne during intubation and can infect the whole operating room for hours. They don’t have a mask for me.
I sent an N95 mask to her by FedEx. It arrived three hours late.
We had just opened IndieBio New York. Our team there never even had a chance to visit the lab before being sent home. But they were working with the state, and it became clear we needed to send Craig to the New York Genome Center in SoHo. His ability to do high-volume testing was more needed there than in San Francisco. He started with all 4,000 people at the United Nations.
Working with Sean O’Sullivan, the managing general partner of our firm, we decided to announce publicly that we would fund eight COVID-19 initiatives.
We got drowned in applications. Everybody needed money. Few VCs were open for business. The team did fifteen to twenty Zoom calls a day. Decoy strategies at the heparan sulfate receptor. Protein degraders. Vaccine platforms. Llama antibodies. Antivirals from plants. Sanitizer tech that used nothing but water and charged ions. I’ve never seen a team absorb so much information, so fast, and make decisions on the fly about what they believed was our best chance.
Exosomes, engineered to rescue lung function in patients who can’t breathe. Mickey needs 60 days. We’re in.
Some people checked the stock market ten times a day. I checked Nextstrain to follow the mutations and migrations. Both are a kind of Rorschach test.
Message posted on IndieBio Slack:
Also if you join by video, please dress up. Haha. Theme is that it is the year 3020 and the human race has been in isolation for 1000 years.
Message posted on IndieBio Slack:
Shit! Ryan Gosling’s Butter Sacrifice party is popping! The tunes are crazy!
Franco called from IndieBio. Half his team just tested positive.
Everyone says this started in bats. And that as long as there are bats, there will be viruses spilling over into humans. But parts of that story are missing.
Bats are the only mammal that flies. Flying raises their heart rate so high (up to 1,000 beats per minute), and they burn so much energy, that the DNA damage created would kill anything else. So along with the ability to fly, bats evolved more powerful DNA repair mechanisms. Their genome has a second copy of P53, the guardian of the genome, which patrols their DNA for mutations. They also express far more interferons. These protect and repair the bat genome so well that bats can also handle all the genetic chaos that viruses create. The viruses will live in bats, without tearing them apart.
Once these viruses spill over to humans, it’s like LeBron James showing up at the local pickup court. It’s too easy. The virus has evolved to compete against far superior bat defenses. Against our weaker defenses, the virus carves us up.
But what’s missing is this: Bats don’t normally infect humans. That’s why this happens rarely. Bat genomes are so good at keeping viruses in check, that most of the time, bats are no danger to humans.
It’s only when bats suffer immunological stress, and their viral load goes way up, that they get sick and can pass their viruses to humans. One of the most common stresses, recently, is loss of habitat. Deforestation, urban development, and arid wetlands.
So this didn’t start with bats. This started with whatever caused the bats to get sick.
Everyone is looking for a drug. But the body is better and faster at designing drugs than any pharma company.
Mutation is normally bad for the body. But we actually have little tiny laboratories in our bodies where we turn on hypermutation when something foreign gets in, like a virus.
We do this in a controlled, safe setting—on a particular stretch of the genome in B lymphocyte cells. This is where the body invents antibodies. The hypermutation is called V(D)J recombination. Variable, Diversity, and Joining. Every time the B cell divides, short code chunks of Vs, Ds, and Js randomly recombine. The genetic proofreaders don’t interfere. The body keeps recombining and recombining until—randomly—one works. If an antibody latches on to the virus, all sorts of signals ramp up, and cells clone the antibody rapidly, like a drug factory. These antibodies mark cells for destruction.
Every single person who gets the virus has to invent their own antibodies. It’s a race: Can your body hypermutate a drug to save you before the virus turns your blood vessels into pink slime?
Someone started tailing me. I tried to shake them in the baking aisle. At the grocery store, it was like a zombie film. In the vegan aisle, the shelves were full. I lost him there.
In Iceland, my family was losing their jobs. The government was testing people randomly, calling them out of the phone book. Ten percent of the country had been tested, so the media was reporting how Iceland hasn’t sheltered in place. But according to our family, nobody was leaving the house. Except to go out and shoot caribou.
I missed being at IndieBio. And even though I wasn’t going to actually leave IndieBio for three more months, being sheltered at home made me aware of what I’d miss the most. It’s how the day starts—how almost every day at IndieBio starts.
I park across the street, step over a whiskey bottle and a syringe, give a hug to whoever opens the door, and descend the steel staircase to the Ivory Basement. The distance to my desk is about the same as a fashion show runway. High fives and more hugs, quick updates, then the team rolls out for coffee. We sit outside on Market Street, the city’s raw spectacle rolling in ecstasy at our feet. We tell personal stories. The drama at group houses. The parties we can’t unsee, even if we wish to. We triage the companies we’re incubating. It feels so good to spend time together. Then we start brainstorming. Maybe it’s how plant cells use gravity to know up from down. Or tax policy in India. Or someone declares the amount of joules in the chemical bonds of a pound of body fat. Somehow, the conversation leaps topic to topic with every exchange, and we always end up talking about something we never could have predicted even a minute earlier. It doesn’t get better.
Melanie had made antibodies against Zika when she was at IndieBio. She believed she could do it again against this virus. There were 23 companies trying to invent the perfect antibody, and a dozen more trying to design one with a supercomputer. “They’re slow,” Melanie said. “They start in humanized mice, then hope what they get works in humans. It takes tons of repetition and adjustment. In a computer, you can design an antibody in days. But you have no idea if it will have off-target effects, so that testing takes months and months.” Melanie said she could do it in 32 days.
Melanie’s approach was truly unique. Her company, Prellis, was the world leader in 3D-printing human organ tissue, using lasers and stem cells. Her goal for Prellis was right out of a science-fiction movie: She wants to print a new liver for patients when their liver is shot. She was getting close. She’d been making mini-livers.
But this was wartime. “I can make dozens of mini-lymph nodes, little immune systems. I’ll inoculate them with the virus. They’ll create antibodies just like they would inside a human body. I’ll screen the antibodies for which works best.”
In a week, the lymph nodes were printed. A week later, inoculated. One more week, and the miracle of V(D)J recombination was generating antibodies to the virus.
Collectively, the search for remedies is like trying to defuse a bomb that you’re carrying in your own hands—while simultaneously running a marathon.
Franco says his team is not positive. It was a false alarm. All the more need for his far more accurate test.
My daughter asks me how talking on the phone can help stop the virus.
One day we will go back to normal. But I’ll fondly remember the girls Zoom-bombing me on my calls, taking family walks in the rain, and losing “name the animal” to my five-year-old.
2
“World’s Supermarket” Returns as Epidemic Eases in China The Star
Once upon a time, I lived and worked in Shanghai, China.
I saw a country, an entire nation, in the midst of rebuilding itself, almost overnight. It was a society coming out of poverty.
It was staggering how much was possible with so little. The sheer scale and speed of this reshaping was warping reality.
My wife and I lived in a local housing development in a Chinese neighborhood. We had one room in a town house, sharing it with two brothers and an old lady. When the temperature dropped below freezing, she would fill the kitchen with steam from a pot, her nose bright red. Thirty tightly packed town houses were divided by narrow lanes that converged on a single exit gate, where a twentysomething guard lived with his family in the gatebooth—a four-foot-by-six-foot shack. It was made of peeling plywood; they had a single hot plate and a bed that folded down from the wall and was held by a chain. In the winter it would freeze, rain, and snow. Every day, the guard’s family would greet us with joy, as we biked out onto Wuyuan Lu and past the wet market on the corner.
I was a designer. I was designing a new beautiful, curved smartphone for Samsung that would cost more than most people I knew in China could afford. I struggled with that. I knew something was being missed. As we crafted the high-end, high-margin blockbuster products for the wealthy, another world was taking shape.
Three hours south of Shanghai was Yiwu. Yiwu market was a mall of wholesale trade goods beyond the imagination. Everything was sold in bulk, in little stores, with factories behind the stores. We walked ninety minutes straight across the mall and never saw the other side. Yiwu had 75,000 stores—150 times more than the biggest malls in America. It’s called “The World’s Supermarket.” A cameraman from CNN spent four days there, and he couldn’t traverse it all. Knockoffs of everything you had ever seen, and everything you had ever imagined, were for sale in bulk, in ten-thousand-unit lots.
You may never have seen Yiwu, but if you’ve traveled at all, you’ve seen what they make. All over the world, in markets from Paris to Jerusalem to Los Angeles, are products made in Yiwu. Later, in Istanbul’s Grand Bazaar, I saw Turkish coffee cezves for sale that I had seen previously in Yiwu. And in Kolkata, India, I saw merchants selling sandals that I had also seen in Yiwu stalls. Yiwu is the backbone of the world economy.
How exactly it was the case that 90 percent of everything in the world came to be made in China, I wasn’t sure. In 1982, the government laid cement boards over a ditch in Yiwu so the first stalls could be erected. We blinked, took a nap, and somehow, it turned into this, a scene from a sci-fi novel on another planet. A new Silk Road had been paved in cheap disposable goods. “Cheap” was the operative word. Most of the world didn’t have much money. They loved cheap.
“Shanzhai” was their word for it. To copy. Counterfeit, without shame. It was not just to replicate products. It was to replicate a notion of living, influenced heavily by the West. I saw entire suburban tract mansion suburbs pop up in months. McMansions. Children on bicycles. Everything but the milkman and Girl Scouts at the corner selling lemonade.
I remember coming back from Ningbo, across Jiaozhou Bay. Halfway across the world’s longest bridge, out of the fog rose a tower known as Haitian Yizhou, “the land between the sea and the sky.” The tower was shaped like an eagle. To design such a bridge, to conquer the strongest tidal forces on the planet, took engineers ten years to figure out—before construction began. Why they added to the complexity by erecting a monument that reached into the sky confused me. That was the moment my friend taught me about Da Qi.
Da Qi is a concept that is wrapped up in Confucian masculinity. It’s a kind of generosity of spirit that comes from economic success. It’s almost two ideas at once—both financial prosperity and sharing its bounty. Da Qi means leaving your village and coming back rich. Paying for dinner is a gesture of Da Qi. Giving expensive gifts is a gesture of Da Qi. The government showed its Da Qi everywhere it could.
The Chinese loved massiveness, but they understood that massiveness in a building creates no awe without empty space around it. Da Qi is measured in empty space. The Palace Museum in Tiananmen Square is surrounded by 109 empty acres. The pagoda at the Temple of Heaven is surrounded by 640 acres—six times the size of the National Mall in Washington, DC. Space, empty space, created authority, impossibly grand.
Even in a corner convenience store, merchants would make piles of goods by the entrance, to convey a sense of incredible abundance.
The rebuilding of China was happening before my eyes, in my three years there. Almost none of the buildings and bridges and roads that I used every day had existed a decade prior. It made me believe that transformation on a large scale was possible. A billion people at once could just start over, do it another way.
It was not the China we hear about today, where the government has an eye on everything and everyone. Back then, eight years ago, this world was being built ad hoc, organically. People were risking their livelihoods and their life savings to take the risk to finance it. Yiwu didn’t arise out of a master plan. It grew by experiment. Each stall was an experiment, until the stalls became stores, and factories. It grew fast, it grew blindly, and it grew dense.
China was evolving so fast not because of its master plan, but despite it. A billion people amounted to a billion experiments.
I had a religious studies tutor. He was a monk and a scholar. We met once a week in cafés, and sometimes he came to my office. I was interested in the helix of interaction between Confucianism and Buddhism during the first century CE along the original Silk Road between Northern India and China. It was during that time that Confucianism, which was historically very pragmatic, absorbed some mysticism.
But I was struggling with the clash between my spiritual lessons and the dynamic experiment I saw outside on the streets. The fundamental precept at the core of both religions is that the mind is the path to knowledge and improvement. That wisdom will emerge if you sit still and discern.
There wasn’t a lot of sitting still outside; there was a lot of action. I got frustrated at the chanting and recitation the monk made me do. He didn’t want to be argued with but I did anyway. He didn’t like me questioning him. Finally, perhaps to appease me—to find a bridge between my restlessness and his sacred texts—he laid a quote on me, from a Confucian scholar around 300 CE named Xunzi.
“Practicing is greater than knowing.” Not better than knowing. Greater.
The philosophy of those words may not be self-apparent, so let me unpack them. “Practicing” means trying, it means acting, it means doing. Xunzi—and many philosophers since—made the case that the Doer learns things beyond the reach of the Knower.
It made inherent sense to me, crystallizing a lot of what I’d been riddling on, including the tension between master plans (made by a Knower) and bottom-up self-organization (all the Doers). In me emerged a philosophy of action. When you act, you learn. That kind of wisdom beats the knowledge you read in a book, every time. To really seek answers, you need to act. To really develop your mind, run more experiments.
The night before we left, the old lady downstairs made us dinner. We called her “Teacher Wang.” She took us by hand along Wulumuqi Lu to the wet market, which was under the cover of corrugated steel panels. Everything for sale was still alive, except for the pig faces, peeled off and hung to dry, like masks. Writhing eels, huge toads, coiled snakes. Teacher Wang chose a three-foot-long ribbon fish, which the fishmonger gutted and cleaned, rinsing his cutting board onto the concrete. We tried to pay, but Teacher Wang refused. Minutes later, the fish was chunked and dusted with rice flour, sizzling in Teacher Wang’s wok. Then she covered the fish in a simple braise, with garlic, ginger and spring onion, dark vinegar, white pepper, and soy sauce. She talked about being a teacher, and about her son, and the fortune of the spring weather.
In the morning, when the truck was loaded with our small room’s worth of belongings, the old lady downstairs cried and hugged my wife. We stopped at the guard’s shack. His girls dropped their piecemeal needlepoints to rush outside.
3
Silicon Valley’s New Obsession: Boring-Ass Startups The Hustle
IndieBio erupted just as the Bay Area was kind of getting sick of itself, whining about how everyone was on the make and everybody’s startups were lame. People who worked at Facebook would go out to dinner and express regret that their job was really to sell ads. Everyone made themselves feel better by hosting Social Purpose Parties. This is where you drink, give money, and talk about using blockchain to protect the environment or end poverty. There was a hunger in the Valley for something rad, something uncompromising. Saving the world was everyone’s favorite topic; they talked about it endlessly. But talk grew cheap.
IndieBio wasn’t a Think Tank. It was a Do Tank. That’s what was so refreshing about it.
What Arvind was doing at IndieBio those first years in San Francisco was felt by all but articulated accurately by none. Yes, technically he had created a venture capital fund. But it was more like he had stolen the tricks of capitalism, or misappropriated them, and was using them to rebel against capitalism.
IndieBio had the kind of public profile in San Francisco that a hip-hop record label might have in LA, spinning out emphatic, provocative hits. I’m pretty sure IndieBio was the only venture capital firm with fans. Fans who rooted for their companies to succeed. At night, hundreds of people would show up.
Nobody was making money yet, but they were lighting up the public imagination. At one of the very first public IndieBio events, Arvind was quoted by the Guardian of London saying, “I’m one of the only people in the world that’s eaten a dinosaur.” Technically, it was a mastodon—and it wasn’t mastodon meat, it was a mastodon gummy bear. Which a startup had made from ancient mastodon DNA to show off that animals don’t need to be slaughtered to have gelatin for gummy bears. But all over England, people were reading about a guy in San Francisco who eats dinosaurs.
Genre:
- "Like being a fly on the wall of the world's most interesting dinner party. Spectral, scary, stupefying, and yet strangely optimistic, DECODING THE WORLD is a journey through the weirdness and wondrousness of the natural world, and our precarious place within it. Required reading for restless times."—James Nestor, New York Timesbestselling author of Breath: The New Science of a Lost Art
- "YES! This is it. The Big Book of Answers you've been looking for. It's kind and funny. It explores and explains. Think of it as a guide book to the human animal for the 21st century."—Noah Hawley, creator of Fargo
- "Fascinating and terrifying. Gupta and Bronson bring biotech to the people, demystifying the anxieties of our fraught and fragile times."—Fatima Bhutto, author of The Shadow of the Crescent Moon
- "DECODING THE WORLD is an absolute delight. Bronson and Gupta have tackled complex, often daunting scientific topics and made them come alive for the reader in a way that amuses and enthralls, while also delivering some urgent calls to action. This is one of the most creative, entertaining, and inspiring looks into the future that you will ever find."—Ashlee Vance, New York Times bestselling author of Elon Musk: Tesla, SpaceX, and the Quest for a Fantastic Future
- "Buddy stories have led to number of Hollywood classics, ranging from The Odd Couple to 48 Hours. In DECODING THE WORLD, Po Bronson and Arvind Gupta take us several hundred miles up the California coast for a new buddy story that uncovers the biotech startup world. In these tales of friendship and exploration, Bronson and Gupta show us how biological engineering is emerging as a dominant technology of this century, one that will help change our world for the better."—p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; line-height: 17.0px; font: 14.7px Helvetica; color: #262524; -webkit-text-stroke: #262524; background-color: #ffffff}span.s1 {font-kerning: none}James J. Collins, MIT and Harvard bioengineer
- "These two headed off to explore knowledge, invention, art, superstition, maybe even salvation and have emerged with what looks like the planet's first atlas of apocalypse avoidance."—Jack Hitt, author of Bunch of Amateurs
- "In DECODING THE WORLD, [the authors deliver]...bold visions for the future...Their experiences fuel interesting discussions about pressing issues and trailblazing science. [And] ask us to rethink everything from government sugar subsidies to the ways we test for disease."—San Francisco Chronicle
- On Sale
- Oct 6, 2020
- Page Count
- 352 pages
- Publisher
- Twelve
- ISBN-13
- 9781538734322
Newsletter Signup
By clicking ‘Sign Up,’ I acknowledge that I have read and agree to Hachette Book Group’s Privacy Policy and Terms of Use