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 As the first blog entry got exhausted. My second book |
| Evolution of Love Part 2 |
| She didn't design better enzymes. She let evolution do it—10,000 times faster than nature. Frances Arnold looked at the fundamental problem facing chemistry in the 1980s and asked a heretical question: What if we're doing this backwards? For decades, chemists had tried to design better enzymes through pure logic. They studied molecular structures, ran calculations, predicted which changes would improve function. It was meticulous, rational, scientific. And it almost never worked. Frances, a young chemical engineer fresh out of Berkeley with her PhD in 1985, had a different idea. What if we stopped trying to outsmart nature and just copied nature's method instead? What if we used evolution? Her colleagues thought she was crazy. This wasn't medieval times. This was the late 1980s—the era of rational drug design, computer modeling, precision engineering. In modern science, you didn't just throw random changes at a problem and hope something worked. That was chaos. That was guesswork. Frances called it evolution. "I was viewed somewhat skeptically by gentleman scientists," she later recalled, "who thought that proteins should be designed rationally." But Frances had a response: "I'm not a gentleman and I'm not a scientist—I'm an engineer." And engineers solve problems that work in the real world, not just on paper. So in the early 1990s, Frances Arnold did something revolutionary. She took an enzyme called subtilisin and started breaking it on purpose. She created random mutations in its genetic code. Thousands of them. She put each mutated gene into bacteria and watched them produce thousands of different enzyme variants—most of them worse than the original, some of them complete failures. This was the part that made her colleagues uncomfortable. She was creating mess. Chaos. Failure after failure after failure. But then came the selection. Frances tested every variant to see which ones worked best in organic solvents—environments where natural enzymes normally failed. She threw away the failures. She kept only the winners. Then she did it again. She mutated the winners, created thousands more variants, tested them ruthlessly, kept only the best. Generation after generation after generation. Natural evolution takes millions of years. Frances was running evolution in weeks. In 1993, she published the first successful directed evolution of an enzyme. The response from the scientific community was... skeptical. Some thought her approach was unscientific. Too random. Too messy. Real scientists designed molecules through careful reasoning, not blind trial and error. Frances kept experimenting. And slowly, the results became impossible to ignore. Her evolved enzymes weren't just marginally better—they were doing things no naturally occurring enzyme could do. They were working in harsh industrial conditions. They were catalyzing reactions that didn't exist in nature. She had hijacked evolution itself and made it work 10,000 times faster in a laboratory flask. By the late 1990s, other labs started adopting her method. By the 2000s, pharmaceutical companies were using directed evolution to design better drugs. Chemical manufacturers were using it to create greener industrial processes. Frances and her team kept pushing further. They evolved enzymes to make bonds that don't occur in biology—bonds between carbon and silicon, carbon and boron. They created enzymes that could transform simple sugars into isobutanol, a fuel that could power cars and airplanes. The implications were staggering. For decades, chemical manufacturing had relied on toxic solvents, extreme temperatures, heavy metals. It was efficient but devastating to the environment. Frances's evolved enzymes could do the same chemistry at room temperature, in water, with no toxic waste. They could replace harsh chemicals in laundry detergents. They could manufacture pharmaceuticals more cleanly. They could produce biofuels from renewable sources. She wasn't just making better enzymes. She was making chemistry sustainable. In 2005, Frances co-founded Gevo, a company using engineered yeast to produce renewable fuels. In 2013, she co-founded Provivi, which uses evolved enzymes to create insect pheromones that disrupt crop pests without pesticides. She held over 60 U.S. patents. Her methods were being used in hundreds of laboratories and companies worldwide. In 2011, she became the first woman to win the Charles Stark Draper Prize—the engineering equivalent of the Nobel Prize. She was elected to all three U.S. National Academies: Sciences, Engineering, and Medicine. The only woman to achieve this at the time. In 2016, she became the first woman to win the Millennium Technology Prize—the world's largest technology prize, awarded once every two years. And then, on October 3, 2018, Frances Arnold was asleep in a hotel room in Dallas when her phone rang at 4 a.m. She thought it was one of her sons with a problem. Instead, it was Stockholm calling. She had won the Nobel Prize in Chemistry—the first American woman ever to receive this honor. Only the fifth woman in the prize's 117-year history. Frances was "absolutely floored." She had to reschedule her lecture that day to fly back to California. The world wanted to celebrate the woman who had taught biology to take orders. But here's what made Frances Arnold's achievement so profound: it wasn't just about making better enzymes. It was about changing how we think about solving problems. For centuries, science operated on a simple principle: understand the rules, then design solutions. Chemistry meant knowing molecular structures. Engineering meant precise calculations. Progress meant control. Frances proved that some problems are too complex for pure design. That sometimes the best solution is to set up the right conditions and let evolution find the answer. She called it "humble in the face of nature's superiority." The gentleman scientists who had dismissed her approach eventually came around. One prominent chemist had declared that if her structure for penicillin was right, he'd give up chemistry and grow mushrooms. (He stayed in chemistry and won a Nobel Prize himself decades later.) But Frances's greatest insight went beyond any single molecule. She proved that you don't need to understand everything to create something extraordinary. You need to understand the process. Set up good selection pressure. Test ruthlessly. Keep what works. Repeat. It's how nature created the stunning diversity of life on Earth over billions of years. Frances just compressed it into a laboratory technique that runs in weeks. Today, directed evolution is fundamental to biotechnology. New cancer treatments. Biodegradable plastics. Enzymes that can break down environmental pollutants. Sustainable alternatives to petroleum-based chemicals. Frances Arnold didn't just invent a technique. She gave humanity a new tool for facing the future: the ability to evolve solutions faster than we can design them. In her Nobel lecture, Frances talked about her career-long concern with "the damage we are doing to the planet and each other." She believed science and technology could help mitigate environmental harm, but only if we had "good, economically viable alternatives to harmful habits." That's what directed evolution provides: chemistry that works with biology instead of against it. Solutions that are economically practical and environmentally sustainable. Frances Arnold is now the Linus Pauling Professor at Caltech. She sits on President Biden's Council of Advisors on Science and Technology. She serves on Alphabet's board of directors. But she's still running experiments in her lab. Still evolving enzymes. Still pushing the boundaries of what biology can do. Because Frances Arnold learned something fundamental: discovery isn't about having all the answers upfront. It's about trust—in curiosity, in failure, in the unpredictable brilliance of evolution itself. She didn't just evolve enzymes. She evolved the way science imagines possibility. She proved that sometimes the smartest thing you can do is admit you're not smart enough to solve a problem through pure logic—and let evolution solve it instead. Nature spent 3.7 billion years perfecting the art of adaptation. Frances Arnold just gave us the keys. |
| In 1957, Fortune magazine called him the richest living American—worth over $1 billion. Inside his English mansion, there was a payphone. Guests had to drop coins to make calls. The 1950s. J. Paul Getty had become one of the wealthiest men on Earth. He owned oil fields across three continents. A 72-room Tudor mansion in England called Sutton Place. Art collections that would eventually fill museums. His wealth was estimated at $1.2 billion—equivalent to roughly $12 billion today. And inside his palatial estate, there was a payphone in the hallway. It wasn't a joke. It wasn't ironic. If you were a guest at Sutton Place and wanted to make a phone call, you dropped coins in the slot. Reporters were baffled. Friends were embarrassed. The public was fascinated and appalled. How could the richest man in America make his guests pay for phone calls? Getty's explanation was characteristically blunt: "People respect what they pay for." But there was more to it. The payphone served multiple purposes—Getty could deduct business calls for tax purposes while ensuring guests' personal calls didn't inflate his bill. It was accounting precision disguised as eccentricity. The payphone became the most famous symbol of Getty's extreme frugality. But it wasn't isolated. Getty clipped coupons from newspapers religiously. He reused envelopes. He tracked every expense to the penny. He wore the same suits for years. He stayed in modest hotels. He negotiated every transaction, no matter how small. His friends were mystified. Here was a man who could buy anything—yet he lived like someone terrified of poverty. "Miserly," the press called him. "Eccentric." "Pathologically cheap." But Getty insisted his habits weren't about greed—they were about discipline. Born in 1892 in Minneapolis, Getty grew up comfortable but not wealthy. His father was an attorney who'd gotten into the oil business. Young Paul worked in oil fields as a teenager, learning the industry from the ground up. He saw fortunes made and lost on speculation, on borrowed money, on reckless confidence. By his early 20s, he was buying and selling oil leases himself. And he developed a philosophy: never borrow what you can't repay. Never spend what you haven't earned. Study every deal obsessively. While rivals took on massive debts to expand quickly, Getty reinvested profits slowly and methodically. While others flaunted wealth to impress investors, Getty lived modestly and let his balance sheet speak. When the 1929 crash devastated the oil industry, Getty was positioned perfectly—he had cash reserves while competitors drowned in debt. He bought oil companies at bargain prices while others were forced to sell. Through the 1930s and 1940s, he quietly accumulated assets. By the 1950s, when oil demand exploded, Getty's investments made him spectacularly wealthy. But the mindset that built the fortune never changed. He still tracked every penny. Still clipped coupons. Still installed that infamous payphone. "Wealth demands vigilance, not vanity," he believed. Getty saw extravagance as a warning sign—people who spent carelessly were people who'd eventually lose everything. Frugality wasn't deprivation; it was insurance against complacency. His critics pointed out the obvious: What's the point of being the richest man in the world if you won't spend money? Getty's answer was more philosophical than expected. He didn't measure wealth in possessions but in control. In options. In the freedom from dependency. Money wasn't for spending—it was for security and power. The same discipline that made him wealthy also isolated him. His five marriages all ended in divorce. His relationships with his children were famously strained. And then came 1973. His grandson, J. Paul Getty III, was kidnapped in Italy. The kidnappers demanded $17 million ransom. Getty refused to pay. He suspected it was a hoax. He believed paying ransoms encouraged more kidnappings. He wouldn't show weakness. The kidnappers cut off the boy's ear and sent it to a newspaper. Only then did Getty agree to pay—but he negotiated the price down to $2.2 million. And he loaned his son the money at 4% interest. The public was horrified. Getty's reputation shifted from "eccentric billionaire" to "heartless miser." But Getty saw it differently. Even family couldn't exempt him from his principles. It was a brutal calculus—and one that haunted his legacy. Yet in death, Getty's contradictions became even more apparent. The man who installed a payphone in his mansion left behind an art collection worth billions. The man who clipped coupons founded the J. Paul Getty Museum—one of the richest art institutions in the world, with an endowment of over $1 billion. The museum, free to the public, houses priceless art. It's a cultural treasure—built on the same disciplined accumulation of wealth that Getty was mocked for during his life. J. Paul Getty died in 1976 at age 83. He left behind a fortune, a museum, and a reputation as either the most disciplined businessman of his era or the most miserable miser who ever lived. Perhaps both are true. Getty proved something uncomfortable: that extreme wealth and extreme frugality aren't opposites—they're often partners. That the habits that build fortunes (discipline, vigilance, skepticism of excess) don't disappear just because you've succeeded. That saying "no" to spending—even when you can afford anything—can be its own form of power. The richest living American in 1957 made his guests pay for phone calls. It wasn't poverty. It was philosophy. And whether you call it discipline or dysfunction, it built an empire—and a museum that will outlast both his fortune and his reputation. Sometimes the richest person alive is the one who knows how to say no. Even when they don't have to. |
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