The epidemic was by then in its ninth year, and there were no effective treatments. A diagnosis of HIV was a death sentence. New York and San Francisco were cities of ghosts. Meanwhile, disputes over patents, credit, reagents, and nomenclature cleaved the research community into hostile camps. Most drug companies, profiting mightily from marketing pills for chronic diseases, viewed finding a cure for AIDS as not worth the investment or the trouble. Militant patient advocates would soon pour pig’s blood on Wall Street investors to spotlight the industry’s indifference and greed.
A few leading researchers protested that a self-serving orthodoxy was impeding the flow of new ideas, slowing progress. The Nobel laureate David Baltimore directed a virology institute affiliated with MIT. At 32, he had independently discovered an enzyme essential for the reproduction of retroviruses such as HIV, which spread by inserting their genes into the DNA of host cells and hijacking the cells’ chemical machinery to make copies of themselves. Few investigators were more qualified or better positioned to understand how to stop HIV from spreading.
In 1989, Baltimore proposed a Manhattan Project against AIDS—an all-out, government-led crash program modeled on Washington’s successful effort to harness Big Physics to build a nuclear weapon ahead of Germany and in time to drop two atomic bombs on Japan, ending World War II. As I tracked down dozens of senior scientists for my magazine story, I discovered that no one supported him.
Their opposition was defining for the country—and for me. It would be another six years before the first effective AIDS drugs would be approved for patients. The complete public shunning of Baltimore’s call for a sense of responding to a national need with a federally managed, all-hands collaboration jolted me. I was ignorant and naive about the nature of science and scientists. I needed to understand much better why appealing to cooperation and self-sacrifice in medical research elicited only widespread indifference and scorn. I needed to know how commercial medicine, Wall Street, the federal government, and academia align and interact regarding our health and welfare, particularly in a crisis.
If I ever hoped to explore the process for discovering new medicines and making them accessible to people who need them, I got my chance later that year, the same month the Berlin Wall came down, ending the Cold War and anointing the United States the victor. I persuaded the founder of Vertex Pharmaceuticals, Joshua Boger, to let me try to convince the board of directors of his fledgling drug company to have me embedded while they launched their business. Boger had left Merck to build Vertex in a converted construction garage in Cambridge, Massachusetts. He believed that he could do better starting out on his own from scratch. A half-dozen up-and-coming Merck researchers had soon defected to join him. After convincing the directors that I could be trusted not to give away scientific secrets and that I would stay out of everyone’s way, I was fortunate enough to go along for the ride—twice—producing, 20 years apart, two acclaimed backstage accounts of American Pharma.
Drugs are molecules. They affix themselves along critical points in the pathway of disease. They unlock the unknowably complex biological activity within us to make us feel better, allay our symptoms, or prevent us from becoming sick. They save our lives. As they are imprecise, they also produce unwanted, often toxic side effects. Many are powerfully addictive. New drugs are far too expensive and inaccessible, but manufacturers have no incentive to sell cheaper alternatives. Those that require a doctor’s prescription give physicians a vested stake in promoting their use, leaving the rest of us to wonder whose interests are served when we take them.
For more than a century, ever since the German biochemist Paul Ehrlich posited such molecular interventions, the ultimate challenge for researchers has been finding and developing novel patentable molecules. Following Ehrlich’s prophecy, German dye makers discovered a rich vein of such carbon compounds in noxious coal tar, and for a generation Germany led the world in breakthrough drugs. Then, during World War II, America’s pharmaceutical manufacturers unearthed the mother lode: microorganisms. They unleashed a flood of antibiotics that they had discovered by screening foul-smelling fermentation broths for hits—biologically active molecules produced by good bugs to kill bad bugs—that could be developed into drugs against not only microbial infections but a host of other illnesses. Big Pharma was off and running.
Boger and his scientists intended to show that safer, more effective, more transformational drugs could be discovered and systematically improved by assembling them atom by atom based on information about how molecules bind and interact—so-called structure-based design. “Merck’s first team making drugs for the hardest diseases with computers,” as his chief business officer often distilled it for potential investors. Boger swore that Vertex would never work in AIDS, partly because Merck had entered the field and partly to avoid the sordid squabbles that had besmirched AIDS research. But the scientists made him reconsider. By committing to compete with Merck, he stuck his neck out far in the race for an AIDS drug and he pushed the scientists hard to prove that they had made the right call.
It was his messianic belief in his method and in himself and the scientists that turned him around. “The data took us there,” he told me. “The opportunity took us there.” His researchers’ passion beyond explanation convinced him that Vertex could design a better drug than Merck with a handful of chemists in much less time. Once he reversed himself, he was all in. “Joshua’s found a new religion,” one of his former bosses at Merck told me in 1990. “I just hope he doesn’t forget that the old religion, in its way, was incredibly successful.”
The Age of Cures excavates and untangles the roots of the old religion of natural product screening that led to America’s 80-year-long preeminence in drug research. This religion, part science and part faith, coalesced from urgently assembled parts during the Second World War, a by-product of the great national mobilization that has propelled the nation’s progress ever since.
For nearly 20 years before that, as society wrestled with repressed horror and grief over the 1918 flu pandemic, the deadliest contagion in history, and the grinding hardships of the Great Depression, medical science stagnated. Human biology was a black box. Intractable questions about treating illness were far too big and complex for small, siloed, underfunded laboratories to make much progress.
Disease foundations, university labs, medical schools, and research clinics collaborated loosely. But the country had no scientific order, no institutions, no channels for funneling its newfound bounty into making itself healthier. No direction. Most prominent investigators went begging for funds. Merck, a fine-chemical company with pharmaceutical aspirations, manufactured several vitamins. But the state of the art in using chemical compounds against sickness remained a bet on progress—a creed, not a practice. Unchecked sepsis from even the smallest cuts, scrapes, and blisters could still kill you. Ehrlich’s promised land of chemotherapy for everything from scratchy throats to brain cancer was shrouded in failure.
In 1941, as the United States vacillated toward war, President Franklin D. Roosevelt’s science adviser, Vannevar Bush, invented a new federal agency to harness American science to meet the challenges of defeating Germany’s vaunted scientific empire. Bush’s Office of Scientific Research and Development, or OSRD, created the Manhattan Project. It also built a second, alternate infrastructure for empowering scientists to meet the nation’s most pressing public health needs.
To produce enough penicillin for D-Day, OSRD enlisted a coalition of private and public laboratories to share research and resources, the formula David Baltimore urged against AIDS. Boger’s father in science, the visionary medicinal chemist Max Tishler, devised Merck’s pathbreaking method of fermenting, formulating, purifying, and delivering penicillin to the first patients to receive it. He soon repeated the feat with the first effective treatment for tuberculosis. Near the end of the war, Bush submitted a report on the lessons learned from wartime research. His manifesto Science, the Endless Frontier urged extending the partnership among government, academia, and business into peacetime.
Large and sustained government investment in public and private research employing federal contracts and competitive grants seeded the ground for the emerging biomedical ecosystem. Intentionally diffuse but also interconnected, the American system of science defeated a monolithic German superpower. Of course, it had crucial assistance from Adolf Hitler, who viewed physics as “Jewish science” and purged the Third Reich of its best scientists. The state-run IG Farben’s organic chemists were too preoccupied with meeting the escalating demands for Gigas Zyklon-B for the Nazi death camps to worry about novel anti-infectives.
How did we get here? How did a system for eliciting the best results in the war against disease, a system that out-thought and out-organized Nazi Germany and Soviet Russia, come under a wrecking ball swung by an administration hell-bent on fracturing it through politically motivated mass firings, spending cuts, legal threats, disinformation, ruthless immigration enforcement, quackery, and antiscience conspiracy claims and rhetoric and intimidation? It makes no sense. But it’s accelerating at a rate researchers warn may not be reversible.
The Age of Cures explores the prehistory of our medicated world, the period when a revolution in science translated into a cornucopia of wonder drugs discovered by screening soil samples from around the globe. It dramatizes how Merck had become, by the time I met Boger, the most admired company in America year after year—“The Miracle Company,” as Business Week called it in a worshipful cover story. It zeroes in on the pioneers of this revolution and illuminates the formation and controls of the system that Donald Trump, Robert F. Kennedy Jr., and their minions are gleefully trying to smash and destroy.
The quest for better medicines mirrors the other great scientific-political struggle of its time: the race to develop the atom bomb during World War II and the unfolding nuclear standoff during the Cold War. The same alliance that organized our dominant medical and military research, then fomented unprecedented peacetime health, prosperity, and scientific advancement, spearheaded the resistance to the hydrogen bomb and to reactionary, McCarthyist attacks on scientists. The decade that followed crackled with major medical breakthroughs, marketing wars, and political tumult. The controversies climaxed in Washington during the Kennedy years, more than six decades ago—not so far in the past that many of us can’t remember life before it, when the only thing that terrified our parents more than polio was nuclear war. It was the period when America became great at doing science.
Why would a country want to destroy one of its greatest assets? Why would we invite China and other competitors to poach our best researchers and students and then use them to surpass us? It’s unfathomable. Yet it’s true. And it is fast approaching a point when it may be too late.
When COVID-19 hit U.S. shores—when all countries everywhere were hit almost at once—no other country had the depth, breadth, and connectivity of research assets to address it as quickly as the diffuse, government-reliant American system of doing collaborative pharmaceutical research in wartime. Government officials and media voices evoked the Manhattan Project to stress the vaccine program’s great urgency, resolve, cost, and provenance. But it was the penicillin protocols that were faithfully reproduced in Operation Warp Speed, the public-private partnership that had delivered safe, effective vaccines against one of history’s deadliest pathogens in record time. That Trump supported the program, then licensed RFK Jr. to go wild on health, recklessly unwinds our national consensus on the role of medical science in protecting society.
In 2012, after 20 years of hundred-hour workweeks and the efforts of more than a thousand researchers—and burning through more than $4 billion in investment capital—Vertex received FDA approval for the drug that would finally turn enough of a profit to transform the company into an industry powerhouse. I stood in the back of a hotel ballroom in Cambridge, Massachusetts, watching Boger, recently retired as CEO by the board in a palace coup but still a company director, fire up the sales force. He framed the company’s mission as it prepared to go head to head against Merck for the most prized market opportunity in pharmaceuticals as less a clash over science and money than as a pledge to live up to a higher calling.
“Bringing a major drug forward, bringing it out of discovery and into development, then out of development and into the market, bringing it to patients and changing their lives, is . . . the hardest thing that humans can do. Putting a man on the moon? Not . . . so . . . hard. Engineering is an amazing discipline, but it’s also a discipline that succumbs every single solitary time to time and effort. If you give me 20 years and a half-trillion dollars, I guarantee I can put people on Mars and bring them back. I guarantee it. Any of you could guarantee it. But making a new drug that changes people’s lives is almost beyond human understanding.”
Almost, he said. Almost—or just until scientists discover what to do next and teach the world how to apply it. This—the exuberant faith, the expertise, the buoyancy, the gameness, above all the hard-won skills to overcome nature with medicine—is what we risk losing if Washington’s onslaught is successful and the United States becomes the latest scientific empire to succumb to misguided, misinformed, heedless national leaders. The Age of Cures lays out the stakes.
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