How to Nurture the Crazy Ideas That Change the World (Loonshots excerpt)

How to Nurture the Crazy Ideas That Change the World (Loonshots excerpt)

A dozen or so years ago, a friend took me to see a play called The Complete Works of William Shakespeare (Abridged). Three actors covered 37 plays in 97 minutes (including Hamlet in 43 seconds). They skipped the boring stuff. Not long afterward I was invited to give a talk at a business gathering. The topic was my choice, but it could not be related to my job. I presented “3,000 years of physics in 45 minutes”—the eight greatest ideas in the history of the field. I skipped the boring stuff.

That greatest hits show ran on and off until 2011, when the personal hobby crossed paths with a professional assignment. I was asked to join a group developing recommendations for the president on the future of US national research. On the first day, our chairman announced our mission. What should the president do to ensure that national research continues to improve the well-being and security of our country for the next fifty years? Our task, he said, was to create the next generation of the Vannevar Bush report.

Unfortunately, I’d never heard of Vannevar Bush, or his report. I soon learned that Bush developed a new system, during the Second World War, for nurturing radical breakthroughs astonishingly fast. His system helped the Allies win that war, and the United States lead the world in science and technology ever since. Bush’s goal: that the US should be the initiator, not the victim, of innovative surprise.

What Bush did, and why he did it, came right back to one of those eight greatest ideas of physics: phase transitions.

In my new book, I’ll show you how the science of phase transitions suggests a surprising new way of thinking about the world around us—about the mysteries of group behavior. We will see why good teams will kill great ideas, why the wisdom of crowds becomes the tyranny of crowds when the stakes are high, and why the answers to these questions can be found in a glass of water.

I’ll describe the science briefly (skipping the boring stuff). And then we’ll see how small changes in structure, rather than culture, can transform the behavior of groups, the same way a small change in temperature can transform rigid ice to flowing water. Which will give all of us the tools to become the initiators, rather than the victims, of innovative surprise.

Along the way, you will learn how chickens saved millions of lives, what James Bond and Lipitor have in common, and where Isaac Newton and Steve Jobs got their ideas.

In thinking about the behavior of large groups of people in this way, we are joining a growing movement in science. Over the past decade, researchers have been applying the tools and techniques of phase transitions to understand how birds flock, fish swim, brains work, people vote, criminals behave, ideas spread, diseases erupt, and ecosystems collapse. If twentieth-century science was shaped by the search for fundamental laws, like quantum mechanics and gravity, the twenty-first will be shaped by this new kind of science.

None of which changes the well-established fact that physics rarely mixes with the study of human behavior, let alone sits down for a full-course meal, so some sort of explanation is in order. I was born into the field. Both my parents were scientists, and I followed them into the family business. After a few years, like many who follow their elders, I decided I should see other parts of the world. To my parents’ horror, I chose the business world. They responded to my lost academic career with the five stages of grief, starting with denial (telling family friends it was just a phase), skipping quickly past anger to bargaining and depression, before settling into resigned acceptance. I missed science enough, however, that eventually I joined forces with a handful of biologists and chemists to start a biotech company developing new cancer drugs.

My interest in the strange behaviors of large groups of people began shortly afterwards, with a visit to a hospital.

One winter morning in 2003, I drove to the Beth Israel Deaconess Medical Center in Boston to meet a patient named Alex. Alex was 33, with the strong, graceful build of an athlete. He had been diagnosed with an aggressive form of cancer called Kaposi’s sarcoma. Six regimens of chemotherapy had not stopped his disease. His prognosis was poor. A handful of scientists and I had spent two years preparing for this moment. Alex was scheduled to be the first patient to receive our new drug for treating cancer.

When I entered his room, Alex was lying in bed, attached to an IV drip, speaking softly to a nurse. A yellowish liquid, our drug, fed slowly into his arm. The physician had just left. Then the nurse, who had been writing up notes in the corner, closed her folder, waved, and left. Alex turned to me with a gentle smile and quizzical look. The frenzy of activity to get to this day—licensing discussions, financings, laboratory studies, safety experiments, manufacturing checks, FDA filings, protocol drafting, and years of research—melted away. Alex’s eyes asked the only thing that mattered: would the yellowish liquid save his life?

Physicians see this look all the time. I didn’t.

I pulled up a chair. We talked for nearly two hours, as the drug dripped into Alex’s arm. Restaurants, sports, the best cycling paths in Boston. Toward the end, after a pause, Alex asked me what would be next, if our drug didn’t work. I stumbled through some non-answer. But we both knew. Despite tens of billions of dollars spent every year on research by national labs and large research companies, sarcoma treatment hadn’t changed in decades. Our drug was a last resort.

Two years later, I found myself pulling up a chair next to another bed, in a different hospital. My father had developed an aggressive type of leukemia. One older physician told me, sadly, that all he could offer was the same chemotherapy he had prescribed as a resident forty years earlier. Second, third, and fourth opinions and dozens of desperate phone calls confirmed what he said. No new drugs. Not even any promising clinical trials.

There are some technical reasons why cancer drug development is so difficult. So many things have broken down inside a cancer cell by the time it starts proliferating that there’s no easy fix. Laboratory models are notoriously bad at predicting results in patients, which leads to high failure rates. Clinical trials take years to conduct and can cost hundreds of millions of dollars. All these points are true.

But there’s more.

“They looked at me like I was a lunatic,” Richard Miller told me.

Miller, an affable oncologist in his sixties, was explaining to me the reactions of research teams at large pharma companies to his suggestion of treating cancer patients with a new drug he had been working on. It was a chemical designed originally just for laboratory use, for experiments—a tool, like bleach.

Most drugs work by gently attaching themselves to the overactive proteins inside cells that trigger disease. Those proteins act like an army of hypercharged robots, causing cells to go haywire. The cells may start multiplying out of control, like in cancer. Or they may attack the body’s own tissues, like in severe arthritis. By attaching to the overactive proteins, drugs dial down their activity, quieting the cells, restoring order in the body.

Miller’s Piranha

Miller’s drug, however, didn’t gently attach; it was a piranha (irreversible binder, to chemists). It grabbed hold and never let go. The problem with piranhas is that you can’t wash them out of your system if something goes wrong. If they latch on to the wrong protein, for example, they can cause serious, even fatal, toxicities. You don’t give piranhas to patients.

Miller was the CEO of a struggling biotech company. Its first project, developed a decade before Miller’s new drug, hadn’t panned out. The company’s stock price had fallen below a dollar, and it received a delisting notice from Nasdaq, meaning that it would soon be banished from the market for serious companies and transferred to the purgatory of flaky has-beens.

I asked Miller why he persisted with the piranha in that precarious state and despite so many rejections, even ridicule. Miller said he understood all the arguments against his drug. But there was a flip side: the drug was so strong that he could give a very low dose. Miller also served part-time as a physician at Stanford University. He explained that he knew his patients. Many had only months to live, were desperately looking for options, and understood the risks. The potential, in this context, justified the risk.

“There’s a quote from Francis Crick that I love,” Miller said. Crick was awarded the Nobel Prize for discovering, along with James Watson, the double-helix structure of DNA. “When asked what it takes to win a Nobel Prize, Crick said, ‘Oh it’s very simple. My secret had been I know what to ignore.’”

Miller shared the early laboratory results from his piranha with a handful of physicians, who agreed to proceed with a clinical trial in patients with advanced leukemias. But Miller’s investors were not convinced. (Miller: “To this day, if you ask them [how the drug works], they wouldn’t know.”) He lost a boardroom battle and resigned as CEO.

The trial, however, continued. Not long after Miller left, early results came back. They were encouraging. The company began a much larger, pivotal study. Half the patients would receive standard therapy, half the new drug. In January 2014, the physicians monitoring that study, which enrolled nearly four hundred patients, recommended that the trial be stopped. The results were so spectacular—a nearly ten times higher response rate in patients who received Miller’s drug, called ibrutinib, than in patients who received standard therapy—that denying patients in the control group access to ibrutinib was considered unethical.

The FDA approved the drug shortly afterward. A few months later, Miller’s company, called Pharmacyclics, was acquired by one of those large pharma companies that had ridiculed the idea.

The price: $21 billion.

Miller’s piranha was a classic loonshot. The most important breakthroughs rarely follow blaring trumpets and a red carpet, with central authorities offering overflowing pots of tools and money. They are surprisingly fragile. They pass through long dark tunnels of skepticism and uncertainty, crushed or neglected, their champions often dismissed as crazy—or just plain dismissed, like Miller.

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Drugs that save lives, like technologies that transform industries, often begin with lone inventors championing crazy ideas. But large groups of people are needed to translate those ideas into products that work. When teams with the means to develop those ideas reject them, as every large research organization rejected Miller’s piranha, those breakthroughs remain buried inside labs or trapped underneath the rubble of failed companies.

Miller just barely saved his idea. Most loonshots never get the chance.

There’s something at the core of how large groups behave that we just don’t understand, despite the mountains of mind-numbing print written on the subject. Every year, glossy magazines celebrate the winning cultures of innovative teams. Covers show smiling employees raising gleaming new products like runners raising the Olympic torch. Leaders reveal their secrets. And then, so often, those companies crash and burn. The people are the same; the culture is the same; yet seemingly overnight, they turn. Why?

Articles and books on culture have always felt squishy to me. I hear culture, I think yogurt. For example, one popular book, typical of the genre, identifies a handful of top companies based on their stock price performance and then extracts from their similarities squishy lessons on creating a winning culture. One of those companies happens to be Amgen, a biotech company I know well. Among the Amgen lessons extracted: “By embracing the myriad of possible dangers, they put themselves in a superior position.”

The real story with Amgen is that after a couple of years in business, the company was nearly bankrupt, all its initial projects (including a chicken growth hormone and pig vaccines) had failed, and time was running out on a final project, a drug to stimulate the growth of red blood cells. A handful of companies were pursuing the same goal. Amgen got to the finish line just ahead of its competitors. Much of that was due to a University of Chicago professor named Eugene Goldwasser. Goldwasser had worked on the problem for twenty years and held the key to winning the race: an eight-milligram vial of purified protein, painstakingly extracted from 2,550 liters of human urine. The purified protein contained the code to making the drug. He decided to give that vial to Amgen rather than its main competitor, Biogen. Biogen’s CEO had refused to pick up the check for dinner one night.

The drug, called erythropoietin, or epo for short, turned out to be far, far more successful than anyone, including Amgen, imagined—eventually bringing in $10 billion a year. Amgen had won the drug-discovery lottery. Once it had the drug, Amgen sued everyone else in the business (including its partner, Johnson & Johnson, which had saved Amgen when it was struggling) to stop them from competing. For the next fifteen years, Amgen was unable to repeat its drug-discovery success. Its poor research output, as measured by number of patents awarded, was noted by the culture-analyzing book, which concluded that being “innovative doesn’t seem to matter very much.”

Amgen may not have had good research, but it did have good lawyers. It won every lawsuit, and its competitors gave up. Among insiders, the company was called “a law firm with a drug.”

Useful lessons from Amgen’s story include picking up the check for dinner and hiring good lawyers. But otherwise, extracting culture tips, after the fact, from its terrific stock price performance is like asking the guy who just won the Lotto to describe the socks he was wearing when he bought the winning ticket.

My resistance to after-the-fact analyses of culture comes from being trained as a physicist. In physics, you identify clues that reveal fundamental truths. You build models and see if they can explain the world around you. And that’s what we will do in this book. We will see why structure may matter more than culture.

Excerpted from Loonshots: How to Nurture the Crazy Ideas That Win Wars, Cure Diseases, and Transform Industries. Copyright © 2019 by Safi Bahcall. Published by St. Martin’s Press.

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How to Nurture the Crazy Ideas That Win Wars, Cure Diseases, and Transform Industries

Loonshots reveals a surprising new way of thinking about the mysteries of group behavior that challenges everything we thought we knew about nurturing radical breakthroughs.

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