Viagra Was a Failed Heart Drug: 9 Billion-Dollar Medicines Discovered by Accident

Viagra (Sildenafil) — 1998

In the mid-1980s, a team of Pfizer researchers at their lab in Sandwich, England set out to develop a treatment for angina pectoris — chest pain caused by restricted blood flow to the heart. The compound they synthesized, internally designated UK-92,480, was a PDE5 inhibitor designed to relax blood vessels and increase oxygen supply to the heart.²

It was, by their own admission, a mediocre heart drug. Clinical trials showed minimal improvement in angina symptoms. By 1993, after eight years and millions of dollars invested, Pfizer was preparing to shelve the project entirely.³

Then something unusual happened. Male participants in the trial started reporting an unexpected side effect: erections. More notably, several of them refused to return their remaining pills.⁴

As Dr. David Brown, the lead medicinal chemist on the project, later reflected, the prevailing embarrassment around sexual health nearly prevented anyone from investigating this side effect further. But the trial data was hard to ignore.³

Pfizer pivoted. They redesigned their clinical trials from scratch, recruiting men with erectile dysfunction instead of heart patients. The results were unmistakable — participants reported dramatic improvements, and many asked to continue treatment after the trials ended.⁵

The FDA approved Viagra in March 1998. Within three months, it generated $400 million in U.S. revenue alone.⁵ At its peak, Viagra was bringing in over $2 billion annually and had become the fastest-selling drug in pharmaceutical history. It also spawned an entire class of PDE5 inhibitors — tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) — that collectively treat tens of millions of men worldwide.

Penicillin — 1928

Alexander Fleming didn't set out to change medicine. He went on vacation and left a messy lab behind. When he returned to St. Mary's Hospital in London in September 1928, he found that a petri dish containing Staphylococcus bacteria had been contaminated by a speck of airborne mold. Around the mold, the bacteria had died.⁶

Most researchers would have tossed the dish. Fleming didn't. He identified the mold as Penicillium notatum and published his findings in 1929 — though the scientific community showed almost no interest. It took another 12 years before Howard Florey and Ernst Chain at Oxford figured out how to purify the compound for human use. Even then, the process was so inefficient that gallons of mold broth produced enough penicillin for a single dose.⁷

By the end of World War II, American pharmaceutical companies were producing 650 billion units of penicillin per month. It has since saved an estimated 200 million lives and spawned the entire modern antibiotic industry.⁷

Botox (Botulinum Toxin) — 1987

Botulinum toxin is one of the most lethal substances known to science. It was first identified in the 1890s by Belgian scientist Emile Pierre van Ermengem while investigating a fatal outbreak of food poisoning.⁸

By the 1970s, ophthalmologist Dr. Alan Scott had figured out that microscopic doses could treat strabismus (crossed eyes) by weakening overactive eye muscles. The FDA approved it for that purpose in 1989 under the name Oculinum, which Allergan later rebranded as Botox.⁹

The cosmetic revolution happened by accident in 1987. Canadian ophthalmologist Dr. Jean Carruthers was treating a patient for blepharospasm (involuntary eyelid spasms) when the patient complained that Dr. Carruthers hadn't injected her forehead. The reason? "When you do, my wrinkles go away."⁸

Carruthers and her dermatologist husband Alastair tested their receptionist the next day. The results were obvious. They expected the world to embrace their discovery — instead, the typical reaction was, "You want to inject what into my wrinkles?" Jean Carruthers, now known as the "Godmother of Botox," famously hasn't frowned since 1987.⁸

Botox received FDA approval for cosmetic use in 2002. Today it generates over $5 billion annually and is the most widely performed cosmetic procedure in the world, with over 7 million treatments per year in the U.S. alone.⁹

Ozempic / Semaglutide — 2017

Semaglutide was developed by Novo Nordisk as a GLP-1 receptor agonist to help Type 2 diabetes patients manage blood sugar. The FDA approved it for that purpose in December 2017 under the brand name Ozempic.¹⁰

Then patients started reporting something the clinical trials had technically measured but that nobody fully anticipated: dramatic, sustained weight loss. The drug mimics a gut hormone that signals fullness to the brain and slows digestion — and it turns out those mechanisms are profoundly effective for weight management, not just blood sugar control.¹⁰

The FDA approved a higher-dose version as Wegovy for chronic weight management in 2021. The drug is now being studied for potential benefits in chronic kidney disease, sleep apnea, addiction, and even Alzheimer's disease.¹¹ In 2023, semaglutide generated over $18 billion in revenue for Novo Nordisk, making it one of the best-selling drugs in pharmaceutical history.

Minoxidil (Rogaine) — 1988

The story begins in 1954 at the Upjohn Company (now part of Pfizer), where researchers were looking for a compound to treat peptic ulcers. The drug they developed was a total failure for stomachs. But it showed an interesting effect: it dramatically lowered blood pressure.¹²

Upjohn pivoted to developing it as an antihypertensive and hired Dr. Charles Chidsey at the University of Colorado to run clinical trials for severe hypertension. The drug worked — but it came with an unmistakable side effect. Patients were growing thick hair all over their bodies.¹³

Dr. Chidsey reached out to two dermatologists, Dr. Guinter Kahn and Dr. Paul Grant, who crushed minoxidil tablets into a crude solution of alcohol and water and applied it to the bald patch of a medical student. Within months, the student was growing thick, terminal hair.¹²

The FDA approved topical minoxidil for over-the-counter use in 1988. Today, it remains the most widely used topical hair loss treatment in the world.

Finasteride (Propecia / Proscar) — 1992

In 1974, endocrinologist Dr. Julianne Imperato-McGinley of Cornell University published research on a group of children in the Dominican Republic who were born with a genetic mutation that prevented their bodies from producing the enzyme 5-alpha reductase, which converts testosterone into dihydrotestosterone (DHT).¹⁴

What she found was striking: these individuals, known locally as "güevedoces," grew up with small prostates and no male-pattern baldness. Roy Vagelos, then head of research at pharmaceutical giant Merck, saw the study and had an idea: what if you could replicate that effect with a drug?¹⁴

Merck developed finasteride, which blocks 5-alpha reductase and slashes DHT levels. It hit the market in 1992 as Proscar (5 mg) for enlarged prostate. But patients kept reporting the same side effect: their hair was growing back. In 1997, the FDA approved a lower dose (1 mg) as Propecia for male-pattern hair loss.¹⁵

Over 9 million prescriptions are now written for finasteride annually in the U.S. alone.¹⁴

Warfarin (Coumadin) — 1954

In the 1920s, previously healthy cattle across the northern United States and Canada began dying from mysterious internal hemorrhages. Veterinarians eventually traced the cause to moldy sweet clover hay: the mold was producing a compound that prevented the animals' blood from clotting.¹⁶

Biochemist Karl Paul Link at the University of Wisconsin-Madison spent six years and performed roughly 10,000 blood coagulation tests before his team isolated the responsible compound in 1939. They then synthesized hundreds of analogs — the 42nd of which Link named "warfarin" after the Wisconsin Alumni Research Foundation (WARF) that funded his work.¹⁷

Warfarin first went on the market in 1948 — as rat poison. It was incredibly effective because it was slow-acting; rats didn't become bait-shy after the first nibble the way they did with strychnine.¹⁷

The medical pivot came after a young Army recruit attempted suicide by ingesting a large quantity of warfarin rat poison — and survived with treatment. His doctors realized that at controlled doses, the compound could prevent dangerous blood clots in humans. Warfarin sodium was approved for medical use in 1954.¹⁷

A year later, President Eisenhower suffered a heart attack and was treated with warfarin. The media coverage launched it into widespread use. Today, roughly 100 million warfarin prescriptions are written globally each year.¹⁸

Chlorpromazine (Thorazine) — 1954

Around 1950, French surgeon Henri Laborit was searching for an antihistamine that could calm patients before surgery and reduce surgical shock. One compound he tested, chlorpromazine, had such a profoundly calming effect that Laborit recognized its potential for something far beyond the operating room: treating psychiatric disorders.¹⁹

He was right. Within a few years, chlorpromazine was approved as the world's first antipsychotic medication. Its impact on psychiatry was seismic. State psychiatric hospitals, which had been growing for over a century, began to empty. Patients with schizophrenia, bipolar mania, and severe psychosis could, for the first time, be treated with a pill instead of indefinite institutionalization.¹⁹

Chlorpromazine launched the entire class of phenothiazine antipsychotics and fundamentally changed how society treats mental illness. It's been called one of the most important drugs of the 20th century.

Lithium — 1949

In the late 1940s, Australian psychiatrist John Cade was investigating whether a toxin in the urine of manic patients might be responsible for their symptoms. He was injecting guinea pigs with uric acid dissolved in lithium solution — choosing lithium simply because it made the uric acid more soluble, not because he expected it to do anything.¹⁹

The guinea pigs became remarkably calm. Cade tried it on his most severely manic patients. The results were dramatic: agitated, psychotic patients who had been institutionalized for years became stable enough to return home.

Lithium — element number 3 on the periodic table, a simple ion that cannot be patented — remains the gold standard treatment for bipolar disorder more than 75 years later. Because no pharmaceutical company can own it, it never became a blockbuster in the commercial sense. But in terms of lives saved and suffering prevented, it's one of the most important drugs in the history of medicine.