The 10 Most Important Drugs
These breakthrough drugs made medicine modern.

By Daniel DeNoon

Reviewed By Brunilda Nazario, MD
WebMD Feature

What are the most important medicines ever made?

WebMD asked experts to nominate drugs for membership in this exclusive club. Some got in by a unanimous vote. Others were endorsed by some but blackballed by others.

What makes a drug "most important?" Different things, says John Swann, PhD, a historian at the FDA.

"You have to look at this issue not just as thinking of one drug that treats one kind of patient, but of how the drug changed whole infrastructure of the drug industry and the practice of medicine," Swann tells WebMD.

That's true, agrees Trevor Stone, DSc, head of pharmacology at the University of Glasgow. Stone is author of the recent book Pills, Potions and Poisons: How Drugs Work.

"Two things make a drug important: First, that the drug is or was used to treat a large number of people with a range of problems," Stone tells WebMD. "And second, because a drug has led the way, showing it is possible to treat a disease. These drugs spurred the pharmaceutical industry to further research and innovation. If you don't have a starting drug, you don't know what is possible -- and you can't take it on from there."

So which are the 10 most important drugs? Before reading on, think about which drugs you would choose.

In addition to Stone and Swann, WebMD also spoke with two other experts:

Leslie Z. Benet, PhD, was the first president of the American Association of Pharmaceutical Scientists (AAPS). He's professor and former chairman of biopharmaceutical science and pharmaceutical chemistry at the University of California, San Francisco.
Medical historian Stephen Greenberg, PhD, is coordinator of public services for the History of Medicine division of the National Library of Medicine at the National Institutes of Health in Bethesda, Md.

1) Penicillin: First on All Lists

"At the top of my list is penicillin," Stone says. "As the first antibiotic, it pointed the way to the treatment of microbial disease. Without penicillin, 75% of the people now alive would not be alive because their parents or grandparents would have succumbed to infections. The effects of a drug like this are absolutely mind-boggling."

No other drug changed the world quite like this.

"If you were to ask what is the most important drug -- just one -- I'd say penicillin," Greenberg says.

Benet says the drug made a stark difference: "Before penicillin, if you had a serious infection, you died."

Ironically, careless use of penicillin -- and many of the drugs that came after it -- allows germs to develop resistance. It's a race - and the bugs are catching up.

"We are at a crossroads," Greenberg warns. "We keep on coming up with newer and hotter antibiotics, and yet we already wore out the basic ones. So you get into the question of whether the pharmacology people will be able to keep up with the change in the bugs they are fighting. That is going to be really the cutting edge of the future."

2) Insulin: The First Hormone Therapy

Patients with advanced diabetes can't use the energy stored in their bodies. No matter how much they eat, they starve. Why? Their bodies stop making a hormone known as insulin, needed to convert sugar into energy.

Diabetes used to be known as "the sugar sickness." The only treatment was to give patients a near-starvation diet. They got only as much food as they could metabolize. They soon wasted away and died.

Canadian researchers Frederick Grant Banting, MD, and Charles Best, then a graduate student, first identified insulin in 1921. In 1922, a Canadian patient received the first successful treatment with insulin extracted from an animal. Demand for the new miracle treatment quickly outstripped supply, but pharmaceutical companies soon ramped up production.

"Insulin can completely change the lives of diabetes patients," Swann says. "If you look at what was available to people who suffered diabetes before insulin, those diets were just horrible. People with diabetes didn't have too long to live. Insulin is a great example of what can be accomplished in terms of collaboration between industry and academic researchers."

Insulin proved to be a hormone. As such, it's the grandfather of all other hormone-replacement therapies.

3) Smallpox Vaccine, Polio Vaccine

OK, so vaccines aren't really drugs. But the experts argue that preventive medicine has to be taken into account. And few preventive medicines have had the impact of the smallpox and polio vaccines.

Smallpox is by nearly universal acclaim foremost among the most dreadful scourges of humanity. Thanks to vaccination, which got its name from the Vaccinia cowpox virus used in the vaccine, smallpox is the first disease wiped from the face of the earth. (That cultures still exist in laboratories is another story).

And polio is on the verge of being the second scourge to be eliminated. Thanks to the vaccine, it's hard now to remember how frightening polio once was.

"Polio really made a major impact," Benet says. "In the 1940s and 1950s, you couldn't go swimming because parents were worried about polio. A huge number of people were affected."

Thanks to the success of these vaccines, modern vaccination succeeds in keeping many other nasty bugs at bay.

4) Ether: The Making of Modern Surgery

Ether has given way to more modern drugs. But its importance can't be overstated, the experts tell WebMD.

"The reason for that is it is the first drug used as an anesthetic," Stone says. "People used to have limbs literally sawn off while they were held down. Ether made it clear that it is possible to have an agent that can depress a person's brain functioning so major operations can be carried out. Since then there have been improved versions of anesthetics."

That cements ether's place among the most important drugs ever.

5) Morphine: Banning the Bane of Pain

Despite the terrible problem of narcotic addiction, a world without morphine would have more suffering, not less.

Morphine is the active ingredient in opium, used from time beyond memory to treat pain. Isolated in the early 1800s, morphine was named after Morpheus, the Greek god of dreams.

"Without morphine, untold numbers of people would have spent their lives in great pain," Stone says. "And it is used after surgery, alleviating a lot of suffering. It is the forerunner of several generations of pain-alleviating drugs. It is one of the great drugs of all time."

Ironically, efforts to create a non-addictive form of morphine led to the creation -- and marketing -- of diacetylmorphine by the Bayer company. Its 1898 brand name: Heroin.

Despite this and other missteps, morphine and its progeny form the basis of modern pain management. Modern doctors no longer see pain as a side effect of disease. They see it as harmful in and of itself. And they see it as treatable.

6) Aspirin: More Than a Headache Pill

"Aspirin was the first drug to show you can treat simple pain," Stone says. "In terms of the number of people who use it, it is more or less crucial for quality of life. Most people in the world have some kind of peripheral pain, muscle pain, or headache or arthritis, just to give a few examples. For those people, morphine would be inappropriate. As an analgesic, aspirin is very important."

Of course, there now are analgesics with similar modes of action. Some work better for some people, and some avoid some of aspirin's side effects. But more than 100 years after its invention, it's still widely recommended -- and widely used.

"I would single out aspirin from all the other [drugs of its class]," Benet says.

Stone and Greenberg note that aspirin is having a revival. It fights inflammation, a process at the core of heart disease and, perhaps, some cancers.

"It's funny that now every man over 40 and every women over 50 is supposed to be taking this 100-year-old drug," Greenberg says.

7) Salvarsan -- The Cure for Lust

Chances are, Salvarsan didn't make your list of most important drugs. But historians Swann and Greenberg say it belongs in the club.

Salvarsan is the trade name for arsphenamine, invented in 1909. It's also known as Ehrlich 606 because it was the 606th compound tested by the legendary German scientist Paul Ehrlich and colleague Sahachiro Hata as a treatment for syphilis. It worked because the arsenic-based compound is a bit more poisonous to syphilis bacteria than it is to humans.

The treatment made people dreadfully ill. But it didn't kill them, which syphilis would eventually do. Some 20 to 40 treatments, over the course of a year, were needed to cure the disease.

"Salvarsan was a specific treatment for a specific disease. This was the promise that lay before the rest of the century," Greenberg says. "You would be hard pressed to leave it off the list."

More importantly, Salvarsan was the first chemotherapy. Most modern cancer drugs work in much the same way. They are poisonous, hard-to-take drugs dosed to kill a disease before they kill the patient.

With Salvarsan, Ehrlich began another modern tradition: the idea that drugmakers have moral responsibilities.

"People threw rocks at his window," Greenberg says. "They said syphilis was God's punishment for fornicators and that Ehrlich was interfering."

8) Psychiatric Medications -- Calming the Troubled Mind

The insane asylums of yesteryear were built to contain people suffering from the severe psychiatric diseases known as psychoses. These drastic diseases brought down upon patients equally drastic "treatments."

The advent of modern psychiatric drugs in the 1950s changed everything. Benet nominates the low-potency antipsychotic drug Thorazine for the top 10 list. Stone prefers Haldol, the first high-potency antipsychotic.

"[Thorazine] allowed us not to have crazy people," Benet says. "It was the first drug for modern psychopharmacology. The only effective one before that was lithium -- but [Thorazine] let you treat people so they were ambulatory instead of putting them into insane asylums."

"[Haldol] was one of the first drugs to bring schizophrenia under control," Stone says. "It acts specifically on the parts of the brain affected in schizophrenia without just depressing the patient and being a sedative."

Greenberg agrees that psychiatric drugs belong in the top 10.

"The social things about the psychiatric drugs have all sorts of modern resonance," he notes. "These drugs led directly to today's deinstitutionalization of schizophrenics and people with mood disorders."

The modern grandchildren of Thorazine and Haldol are the modern "atypical" antipsychotics. These drugs reduce many of the side effects that remain a significant problem for psychiatric patients.

9) Birth Control Pills

Oral contraceptives changed the world, Benet says. Other experts agree. By giving women control over their reproductive system, these drugs had far-reaching medical and social impact.

10) Help for the Heart

Heart patients today owe a lot to two breakthrough drugs: Lanoxin (digoxin) and Lasix (furosemide, also sold as Lo-Aqua).

"Digoxin makes the list, because a lot of people with heart failure would be dead without it," Stone says.

"I had digoxin originally, but I will go with furosemide [Lasix, Lo-Aqua], one of the first loop diuretics -- water pills -- which is still a very important drug for hypertension and heart failure," Benet says. "Heart disease is so important, and furosemide made a major breakthrough. We have better drugs today, but that was the breakthrough in terms of really being effective. We have so many drugs for congestive heart failure now, but a lot of patients can be treated effectively with cheap diuretics."

In terms of preventing heart disease, the new cholesterol-lowering drugs called statins promise to have a huge impact. One of the first of these drugs, Lipitor, makes Benet's list because of its "profound impact on cholesterol lowering."

Other experts say the statins are too new -- with too short a track record -- to put on the same list as penicillin.

More Great Drugs

Every expert who spoke with WebMD has a different list of favorite drugs. Here are some of the notables:

L-dopa. "When it came out it was such a wonder drug for people with Parkinson's disease," Stone says. "In the latter stages, these people are completely unable to move. But give them a shot of L-dopa and they are walking in 15-20 minutes. ... And it is important also for confirming what we knew about the mechanisms of the disease. … We soon will see major advances in Parkinson's treatment. And this is because of the initial success of L-dopa."
Steroids. "Hydrocortisone and other corticosteroids have an enormous range of uses any time control of inflammation and the immune system is needed," Stone says. "There would be a lot of people with a lot of problems if we didn't have this drug."
Viagra. This was a controversial choice. Most experts said they couldn't bring themselves to put Viagra or other drugs to treat sexual dysfunction on the same list as lifesaving medicines. But Stone makes a persuasive case. "Most people would agree a close physical relationship is fundamental to a good quality of life. Yet there are millions of men around the world unable to have sexual activity," he says. "It is creating a huge improvement in these men's quality of life. It has to be on the list."
The Capsule. Once upon a time, a doctor's prescription came as a powder that had to be measured out and dissolved in water or alcohol. This caused not just inconvenience but frequent errors resulting in over- or under-doses. Then Dr. Upjohn created the gelatin capsule. "This allowed individual dosing," Benet says. "It predates the tablet. It is the beginning of individualization in the way we treat patients."
Cyclosporine. Cyclosporine is the first drug to shut down the immune system. "With the advent of cyclosporine you have an effective transplant drug," Benet says. "That allowed transplants to live and not be rejected by the body."
HIV Drugs. Benet nominates the class of HIV drugs known as protease inhibitors. They aren't the first AIDS drugs. But by combining protease inhibitors with other kinds of AIDS drugs, doctors found that they could keep HIV levels so low that patients did not get AIDS. The only reason more experts didn't vote for HIV drugs is that they're saving a place on the list for the still-undiscovered drug that actually cures AIDS.
Ritalin. Greenberg votes for Ritalin as the drug that showed millions of kids with ADHD could have normal childhoods.

What's the next blockbuster drug lurking just beyond the horizon? We'll have to wait and see. But Swann says it's important to support the system that makes new medical breakthroughs possible.

"I hope that people appreciate that the source for new drugs has come, and will continue to come, from a variety of sources," he says. "You have to have support for basic science, or the pipeline will dry up. And there has to be applied work for the phenomenon to continue as it has. All estates of science have an important role. The universities have a crucial role, as do pharmaceutical companies and government, too, to provide support for these organizations that support discovery."

Published Aug. 30, 2004.

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SOURCES: Trevor Stone, DSc, head of pharmacology, University of Glasgow, Scotland; author of Pills, Potions and Poisons: How Drugs Work. Leslie Z. Benet, PhD, professor and former chairman of biopharmaceutical science and pharmaceutical chemistry, University of California, San Francisco; founding president, American Association of Pharmaceutical Scientists (AAPS). Stephen Greenberg, PhD, history of medicine division, National Library of Medicine, National Institutes of Health, Bethesda, Md. John Swann, PhD, historian, FDA, Rockville, Md.

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