Latest / Making Medicine / 250 Years of American Pharmaceutical Innovation | How America Makes Medicine Ep. 1

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250 Years of American Pharmaceutical Innovation | How America Makes Medicine Ep. 1 · Making Medicine

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  Speaker 1: At making Medicine. We're reporting on the headlines, not making
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  Speaker 1: medical recommendations. For personal health questions, always ask your doctor.
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  Speaker 1: Nothing in this episode constitutes investment, financial, or legal advice.
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  Speaker 1: Consult your own advisors before making decisions. Welcome back to
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  Speaker 1: the Making Medicine Podcast, where science, policy and innovation meet.
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  Speaker 1: I'm your host, John Stanford. Today's show kicks off our
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  Speaker 1: How America Makes Medicine seven part series celebrating two hundred
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  Speaker 1: and fifty years of pharmaceutical innovation. This episode walks us
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  Speaker 1: back through time, looking at how the life sciences have
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  Speaker 1: shaped American history. Let's get into the show. Picture an
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  Speaker 1: American medicine chest in seventeen seventy six. Inside you might
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  Speaker 1: find dried herbs, mineral salts, rhubarb, opium based laudanums, smelling salts,
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  Speaker 1: and mercury compounds. Some remedies could ease pain or settle
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  Speaker 1: a stomach. Others were useless, and a few were actively dangerous.
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  Speaker 1: There were no antibiotics, no insulin, no medicines for high
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  Speaker 1: blood pressure, no reliable treatments for cancer.
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  Speaker 2: To the extent we even knew what it was. Physicians
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  Speaker 2: could not see bacteria, certainly couldn't read a genetic sequence
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  Speaker 2: or conduct anything resembling a clinical trial. One of the
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  Speaker 2: men signing the Declaration of Independence that summer was Benjamin Rush,
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  Speaker 2: the only signer with a medical degree. Rush believed deeply
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  Speaker 2: in science and public health, but like even the most
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  Speaker 2: respected physicians of his era, he practiced medicine with an
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  Speaker 2: extremely limited understanding of disease. That contrast offers a remarkable
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  Speaker 2: way to understand the American story. Over the same two
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  Speaker 2: hundred and fifty years in which the United States grew
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  Speaker 2: from thirteen colonies into a modern nation, a global superpower,
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  Speaker 2: medicine moved from jars and crude ingredients to therapies designed
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  Speaker 2: molecule by molecule, and increasingly, patient by patient. This is
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  Speaker 2: the story of two hundred and fifty years of American
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  Speaker 2: pharmaceutical innovation, a story of scientists, patients, entrepreneurs, manufacturers, regulators,
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  Speaker 2: and ideas that sometimes sounded impossible until they worked. This
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  Speaker 2: is how America makes medicine. In America's earliest days, medicines
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  Speaker 2: were often prepared individually by an apothecary. A pharmacist might
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  Speaker 2: grind a plant, mix a powder, or compound a liquid
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  Speaker 2: for a particular patient. There was little standardization. The strength
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  Speaker 2: of a treatment could vary from one preparation to the next.
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  Speaker 2: Labels could make extravagant claims with very little or no
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  Speaker 2: evidence behind them. But during the nineteenth century, the foundations
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  Speaker 2: of the modern pharmaceutical science that we recognize began to emerge.
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  Speaker 2: Chemists became better at isolating active ingredients from natural substances.
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  Speaker 2: Pharmacists began producing medicines in consistent quantities, and new manufacturing
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  Speaker 2: methods allowed treatments to travel farther and reach more people.
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  Speaker 2: The medicine was no longer simply whatever happened to be
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  Speaker 2: mixed in the back of a local shop. It could
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  Speaker 2: be formulated, tested, packaged, and reproduced. That shift from remedy
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  Speaker 2: to reproducible product was fundamental. It was also, in a sense,
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  Speaker 2: anticipated by the founders themselves. Just eleven years after the
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  Speaker 2: declaration of Independence, the Framers wrote a specific incentive for
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  Speaker 2: invention directly into the Constitution. Article one, section eight gives
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  Speaker 2: Congress the power to promote the progress of science and
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  Speaker 2: useful arts by securing inventors the exclusive rights to their
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  Speaker 2: discoveries for a limited time. That single clause the constitutional
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  Speaker 2: basis for the American patent system created the economic logic
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  Speaker 2: that would eventually make modern drug development possible. But let's
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  Speaker 2: not get ahead of ourselves. These new inventions and the
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  Speaker 2: new ability for doctors to propose new solutions also created
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  Speaker 2: a new problem. How could the public, as it got
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  Speaker 2: to know more about medicine, actually trust what was inside
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  Speaker 2: the bottle? The answer became another important part of the
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  Speaker 2: American pharmaceutical innovation model. Scientific progress in the field would
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  Speaker 2: be paired with standards, oversight, and evidence so that Americans
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  Speaker 2: could trust the drugs they were getting. Fortunately, at the
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  Speaker 2: turn of the twentieth century, Congress got involved. The nineteen
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  Speaker 2: hundred and six Pure Food and Drugs Act prohibited certain
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  Speaker 2: forms of misbranding and adulteration. A few decades later, the
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  Speaker 2: nineteen thirty eight Federal Food, Drug, and Cosmetic Act required
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  Speaker 2: manufacturers to demonstrate that new drugs were safe before marketing them.
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  Speaker 2: Was these pieces of legislation and their implementation that began
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  Speaker 2: to put in the minds of Americans that we can
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  Speaker 2: trust the medicines coming from the next generation of manufacturers.
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  Speaker 2: But it would be a few decades later in the
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  Speaker 2: early nineteen sixty when one FDA reviewer became a symbol
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  Speaker 2: of why that rigorous scrutiny would matter. Her name was
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  Speaker 2: Francis Oldham Kelsey, a pharmaceutical company, repeatedly sought permission to
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  Speaker 2: sell pholidamide in the United States as a sedative. Kelsey
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  Speaker 2: was unconvinced by the safety evidence and resisted pressure to
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  Speaker 2: approve it overseas. Tholidamide was linked to severe birth defects
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  Speaker 2: in thousands of children, but Kelsey's insistence on better evidence
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  Speaker 2: largely kept the drug off the American market. The episode
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  Speaker 2: led to the nineteen sixty two Cafalver Harris amendments, which
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  Speaker 2: required manufacturers to provide substantial evidence that medicines were not
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  Speaker 2: only safe but effective. This sets the groundwork for what
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  Speaker 2: we talk about today. How many times on Making Medicine
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  Speaker 2: as a guest talked about safety and efficacy. It's really
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  Speaker 2: telling to think back to that moment in time when
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  Speaker 2: this became a real part of how we think about
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  Speaker 2: medicine today, and it's an important part of the story.
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  Speaker 2: Regulation and innovation are not necessarily opposites. Trustworthy standards can
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  Speaker 2: make innovation more valuable by giving patients confidence that a
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  Speaker 2: medicine has been seriously evaluated, So we should be grateful
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  Speaker 2: as we walk through this history lesson about the time
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  Speaker 2: and energy Francis Kelsey must have taken and pushed back
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  Speaker 2: to prevent a drug that actually had devastating consequences on
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  Speaker 2: children from making it to the American market. It was
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  Speaker 2: an important time for those standards to be taking shape,
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  Speaker 2: because at the exact same time, medicine was beginning to
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  Speaker 2: accomplish things that earlier generations might simply have called miracles.
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  Speaker 2: Consider diabetes. Before insulin, a child with type one diabetes
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  Speaker 2: was often placed on a near starvation diet in an
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  Speaker 2: attempt to prolong life. The treatment could buy time, but
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  Speaker 2: frequently only months. The disease was effectively a death sentence. Then,
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  Speaker 2: in nineteen twenty two, a severely ill fourteen year old
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  Speaker 2: named Leonard Thompson received one of the first successful insulin
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  Speaker 2: treatments in Toronto. The discovery was Canadian, but its transformation
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  Speaker 2: into a widely available medicine depended heavily on American pharmaceutical manufacturing.
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  Speaker 2: Eli Lilly became the first company to commercially produce insulin,
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  Speaker 2: working to purify it, standardize its strength, and manufacture it
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  Speaker 2: as scale That distinction matters. Discovery is the moment something
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  Speaker 2: becomes possible. The pharmaceutical innovation is the longer process that
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  Speaker 2: makes it reliable, reproducible, and maybe most importantly available to patients.
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  Speaker 2: Insulin did not simply add another product to a pharmacy shelf.
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  Speaker 2: It changed the meaning of diabetes. A rapidly fatal disease
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  Speaker 2: became a condition that people could and very much still
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  Speaker 2: live with. That same pattern repeated across the twentieth century,
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  Speaker 2: where chronic disease became something that was no longer life threatening.
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  Speaker 2: But the twentieth century also story of antibiotics that turned
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  Speaker 2: many bacterial infections from mortal threats into treatable illnesses. Vaccines
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  Speaker 2: dramatically reduced diseases that had once killed or disabled enormous
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  Speaker 2: numbers of children. Medicines made organ transplants possible by controlling
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  Speaker 2: our immune rejection, and new treatments reduced deaths from heart
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  Speaker 2: disease and stroke. The broader transformation was extraordinary. In nineteen hundred,
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  Speaker 2: average life expectancy in the United States was about forty
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  Speaker 2: seven years. By two thousand, only one hundred years later,
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  Speaker 2: it had nearly doubled to seventy seven years. Medicines were
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  Speaker 2: not solely responsible. Clean water, sanitation, safer workplaces, and nutrition
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  Speaker 2: played indispensable roles, but pharmaceutical innovation and America Making medicine
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  Speaker 2: became one of the central tools through which scientific understanding
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  Speaker 2: converted into longer and healthier lives. The second half of
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  Speaker 2: the twentieth century would begin with scientists asking an ambitious question,
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  Speaker 2: could we use living cells within our own bodies as
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  Speaker 2: miniature factories to improve health? The answer to that question
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  Speaker 2: launched the biotechnology revolution. In the nineteen seventies, researchers developed
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  Speaker 2: recombinant DNA techniques that allowed genetic instructions to be inserted
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  Speaker 2: into micro organisms. Those organisms could then produce useful human proteins.
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  Speaker 2: Insulin again was a defining example. Traditional insulin came from
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  Speaker 2: the pancreases of pigs and cattle. It worked, but supplies
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  Speaker 2: depended on animal tissue and the resulting insulin was not
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  Speaker 2: chemically identical to human insulin. Scientists at the young biotech
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  Speaker 2: company Genentech used genetically modified bacteria to produce human insulin.
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  Speaker 2: Genetic then partnered with Eli Lilly, which had the manufacturing
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  Speaker 2: experience and infrastructure needed to produce it. Commercially. In nineteen
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  Speaker 2: eighty two, the FDA approved humulin, the first approved medicine
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  Speaker 2: produced using recombinant DNA technology. It was far more than
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  Speaker 2: a new version of an existing treatment. It demonstrated that
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  Speaker 2: scientists could program living cells to manufacture medicine. That idea
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  Speaker 2: opened an entirely new frontier that would dominate the rest
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  Speaker 2: of the century. We engineered hormones, clotting factors, enzymes, and
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  Speaker 2: other biological therapies. It also helped establish a distinctly American
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  Speaker 2: model of biomedical innovation that looks familiar to US today.
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  Speaker 2: University science and entrepreneurial startups backed by venture investment could
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  Speaker 2: then lead the way to established manufacturers and federal regulators,
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  Speaker 2: everyone contributing different pieces of the same process. No single
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  Speaker 2: institution could do everything, but together they could transform a
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  Speaker 2: scientific insight into a medicine use around the world. The
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  Speaker 2: biotech revolution that Genentech kicked off change not only how
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  Speaker 2: medicines were manufactured, but how precisely they could work. One
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  Speaker 2: of its most important tools was the monoclonal antibody, a
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  Speaker 2: laboratory made protein engineered to recognize a specific target. Think
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  Speaker 2: of traditional chemotherapy as an attack on rapidly dividing cells.
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  Speaker 2: It can damage cancer, but it also damages healthy tissue. Often,
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  Speaker 2: a targeted antibody can be designed more like a guided system.
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  Speaker 2: Find a particular feature on a cell attached to it
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  Speaker 2: and block its activity or alert the immune system to attack. Today,
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  Speaker 2: monoclonal antibodies are used not just in cancer, but inflammatory
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  Speaker 2: diseases asthma, osteoporosis, high cholesterol, infectious disease, and many other conditions.
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  Speaker 2: At the same time, combinations of antiviral drugs transformed another
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  Speaker 2: once terrifying diagnosis. In the early years of the AIDS epidemic,
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  Speaker 2: people diagnosed with AIDS might expect to survive only a
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  Speaker 2: year or two. By the mid nineties, though, researchers had
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  Speaker 2: developed highly active anti retroviral therapy drug combinations that attacked
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  Speaker 2: HIV at multiple points in its life cycle. In the
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  Speaker 2: first year after these combinations became the standard of care,
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  Speaker 2: AIDS related deaths in the United States fell dramatically. Today,
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  Speaker 2: people who are diagnosed with HIV can suppress the virus
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  Speaker 2: and live long, healthy lives, and we may even be
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  Speaker 2: on the brink of a vaccine that prevents the spread
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  Speaker 2: of the disease. Altogether. Another takeaway from scientist's reaction to
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  Speaker 2: the AIDS epidemic is that the greatest breakthroughs didn't come
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  Speaker 2: from one dramatic flash of inspiration. It was accumulated knowledge
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  Speaker 2: building on top of another at a time when treating
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  Speaker 2: the disease and figuring out which medicine might work had
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  Speaker 2: to be paired with manufacturing and process innovations that allowed
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  Speaker 2: that medicine to be made at scale. These things happened
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  Speaker 2: not simultaneously and not even necessarily collaboratively, but they show
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  Speaker 2: what can be done when everyone is working together building
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  Speaker 2: on the successes of one another. The nineteen nineties also
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  Speaker 2: helped launch one of the most ambitious scientific projects ever,
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  Speaker 2: sequencing the human genome. The Human Genome project was expected
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  Speaker 2: to take fifteen years and cost roughly three billion dollars,
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  Speaker 2: but it was completed ahead of schedule in two thousand
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  Speaker 2: and three, and for the first time, scientists had a
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  Speaker 2: reference map of the approximately three billion letters in our
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  Speaker 2: human DNA. That map moved medicine towards a new question.
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  Speaker 2: Instead of asking only what disease does this patient have,
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  Speaker 2: researchers could increasingly ask what is driving this disease in
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  Speaker 2: this particular patient. The era of genomic medicine had begun,
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  Speaker 2: and that shift is the foundation of precision medicine that
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  Speaker 2: we talk about today. A tumor can now be analyzed
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  Speaker 2: for genetic mutations that may reveal which treatment is most
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  Speaker 2: likely to work. A rare disease that once went unexplained
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  Speaker 2: may be traced to a single genetic alteration. Some medicines
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  Speaker 2: can be paired with diagnostic tests that identify the patients
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  Speaker 2: most likely to benefit. And now, in certain cases, medicine
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  Speaker 2: is moving beyond treating the consequences of a genetic error
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  Speaker 2: to correcting the error itself. This is the moment of
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  Speaker 2: gene and cell therapies. Gene therapies can deliver functional genetic instructions,
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  Speaker 2: whilest cell therapies can remove a patient's immune cells, re
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  Speaker 2: engineer them to recognize cancer, and return them to the body.
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  Speaker 2: For most of medical history, a medicine was something given
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  Speaker 2: to a patient. Today, the patient's own cells can become
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  Speaker 2: the medicine they need, and more likely than not, that
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  Speaker 2: was to be the tail of the twenty first century
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  Speaker 2: advents in genetic medicine, precision medicine and going deeper and
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  Speaker 2: what we could do to treat rare disease and the
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  Speaker 2: seven thousand or so conditions that exist without a medicine.
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  Speaker 2: But then COVID nineteen appeared, and scientists needed to produce
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  Speaker 2: a highly effective vaccine at a speed that astonished the world.
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  Speaker 2: To many people. mRNA vaccine technology seemed to have arrived overnight,
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  Speaker 2: but it had not. More than fifty years of public
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  Speaker 2: and private research had established the underlying science. Researchers had
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  Speaker 2: studied messenger RNA, methods of delivering it into cells, and
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  Speaker 2: the structure of related coronaviruses. Scientists had also learned how
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  Speaker 2: to stabilize a viral protein in the shape most useful
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  Speaker 2: for generating an immune response. So when the genetic sequence
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  Speaker 2: of the new coronavirus became available, researchers weren't starting from zero.
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  Speaker 2: They were standing on decades of accumulated work. And that's
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  Speaker 2: one of the central truths of the last two hundred
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  Speaker 2: and fifty years. The final breakthrough becomes visible, but the thousands,
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  Speaker 2: if not millions, of experiments underneath it are usually not known.
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  Speaker 2: A vaccine can be administered in seconds, but developing that
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  Speaker 2: knowledge that made it possible, that took us out of
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  Speaker 2: a epidemic took a generation. So what is powered this
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  Speaker 2: two two hundred and fifty years of progress that have
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  Speaker 2: gotten us to where we are today without a doubt.
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  Speaker 2: American curiosity, the willingness to ask questions whose answers may
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  Speaker 2: not be commercially or medically useful for decades, entrepreneurship, and
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  Speaker 2: the willingness to risk time and capital on experiments that
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  Speaker 2: may fail and most likely will fail, in the hopes
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  Speaker 2: that one out of a dozen, if not hundreds, can
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  Speaker 2: move forward. But the American story far beyond medicine is
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  Speaker 2: one about manufacturing and in this case, the ability to
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  Speaker 2: make a promising therapy consistently safely, and that enormous scale,
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  Speaker 2: And at a time when we're seeing global competitors in
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  Speaker 2: the development of new medicines and new compounds, it may
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  Speaker 2: very well be that manufacturing prowess that proves most valuable
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  Speaker 2: in the decades to come. But we can't forget the
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  Speaker 2: important role that regulation has played and the responsibility to
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  Speaker 2: demand meaningful evidence. Think back to Francis Kelcey and how
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  Speaker 2: transformative pushing back on one likely drug ended up saving lives.
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  Speaker 2: And finally, the last two hundred and fifty years wouldn't
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  Speaker 2: be possible without patients, all of us, but especially the
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  Speaker 2: volunteers who participate in clinical trials, often without knowing whether
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  Speaker 2: an experimental treatment will help them personally. Too often medical
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  Speaker 2: innovations had to happen on the battlefield, and too many
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  Speaker 2: times soldiers were the patients for whom some new and
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  Speaker 2: novel treatment had to be discovered. Every medicine carries this
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  Speaker 2: hidden history, this two hundred and fifty years. Behind the
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  Speaker 2: pill in your medicine cabinet are decades, if not centuries,
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  Speaker 2: of chemistry. Behind an injection is a living cell engineered
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  Speaker 2: to produce a human protein. Behind a personalized therapy is
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  Speaker 2: a genome project begun decades ago. And behind nearly every
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  Speaker 2: successful medicine and many of the unsuccessful ones, are experiments
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  Speaker 2: that taught researchers what not to do and pointed them
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  Speaker 2: towards what might work next. As the United States marks
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  Speaker 2: two one hundred and fifty years, pharmaceutical innovation stands among
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  Speaker 2: its most consequential contributions to humanity, and not because every
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  Speaker 2: problem has been solved. Many diseases remain difficult to treat.
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  Speaker 2: Patients still face serious barriers to affordability and access antibiotic
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  Speaker 2: resistance threatens to reverse past progress, and the science of
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  Speaker 2: conditions such as Alzheimer's disease, aggressive cancers, and many rare
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  Speaker 2: diseases remains painfully incomplete. But history gives us reason for confidence.
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  Speaker 2: Again and again. It was American scientists and institutions that
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  Speaker 2: have taken diagnoses that once meant helplessness and replace them
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  Speaker 2: with possibilities. The medicine chest of seventeen seventy six held
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  Speaker 2: substances that could sometimes relieve suffering. The medicine cabinet of
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  Speaker 2: today contains products that prevent disease, control viruses, even replace
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  Speaker 2: missing proteins, and redirect the immune system. The medicine cabinet
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  Speaker 2: of twenty seventy six may contain therapy capable of repairing organs,
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  Speaker 2: preventing inherited diseases before symptoms begin, and treating conditions we
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  Speaker 2: cannot yet imagine curing. The next breakthrough probably already exists
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  Speaker 2: as an observation in a forgotten laboratory notebook, an unanswered
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  Speaker 2: question in a university, or an experiment inside a company
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  Speaker 2: that has not yet succeeded. For two hundred and fifty years,
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  Speaker 2: American pharmaceutical innovation has been the work of turning those
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  Speaker 2: uncertain beginnings into something extraordinary. More time, more health, and
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  Speaker 2: more hope. That wraps up this episode of the Making
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  Speaker 2: Medicine podcast. I'm incredibly excited about our new seven part
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  Speaker 2: How America Makes Medicine series, so be sure to subscribe
• 19:44
  Speaker 2: on YouTube and follow us on other channels to not
• 19:46
  Speaker 2: miss any of the episodes. Thanks for listening, and as always,
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  Speaker 2: keep innovating.