Five Milestone Medicines That Have Transformed the World in the Past Century

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Five Milestone Medicines That Have Transformed the World in the Past Century

Over the past 100 years, the work of chemists in developing new drugs has become a cornerstone of modern medicine.

Recently, in a special edition celebrating its 100th anniversary, C&EN, a publication by the American Chemical Society, looked back at five milestone medicines from the last century.

The article highlights that these five drugs have not only changed medical practice but also revolutionized the scientific process of drug discovery and even human society itself.

Five Milestone Medicines That Have Transformed the World in the Past Century

Penicillin: The Antibiotic that Saved Millions of Lives

Penicillin, the first effective antibiotic against various bacterial infections, emerged as a life-saving treatment for many once-fatal infections.

In 1928, Sir Alexander Fleming first observed that bacteria growth near mold was inhibited in a petri dish contaminated with mold.

Eleven years later, scientists Howard Florey and Ernst Chain at the University of Oxford began validating penicillin’s antibacterial properties in mice and humans, developing methods for its systematic synthesis.

In 1945, these three scientists were awarded the Nobel Prize in Physiology or Medicine for their work related to penicillin’s discovery.

Even today, penicillin remains one of the most commonly used antibiotics worldwide. It is also a covalent drug, capable of forming covalent bonds with target molecules, irreversibly altering their function.

The concept of rational design of covalent drugs has gained increasing attention in recent years, giving rise to groundbreaking therapies and offering new strategies for targeting previously undruggable molecules.

Chlorpromazine: One of the First Drugs to Directly Treat Psychological Disorders

Originally developed to stabilize patients’ emotions during surgical anesthesia, chlorpromazine found a novel application in treating psychiatric patients.

In 1952, French physician Henri Laborit tested the drug’s effectiveness in combination with other treatments on a 24-year-old patient experiencing a psychotic episode.

Within three weeks, the patient recovered to the point of being discharged.

Chlorpromazine’s use spread rapidly among psychiatric patients, and it gained FDA approval in 1954. It was one of the first-generation antipsychotic drugs.

Its introduction marked a significant shift, indicating that mental illnesses could be treated chemically, ushering in the era of psychopharmacology and fundamentally transforming psychological practice.

Oral Contraceptives: The Pill that Revolutionized Society

In the 1920s, scientists knew that injecting animals with reproductive hormones like progesterone could prevent pregnancy.

However, using progesterone directly as a drug posed challenges, requiring high doses through injection or oral administration to be effective.

In 1951, chemists Carl Djerassi, Luis Miramontes, and George Rosenkranz synthesized the first progesterone analog, norethindrone, which was effective at lower doses when taken orally, opening the door to oral contraceptives.

In 1957, the FDA approved the combination therapy of norethindrone and ethinylestradiol for treating menstrual disorders, and in 1960, it was approved as the first oral contraceptive.

By giving women the power of reproductive control, oral contraceptives brought about a societal revolution.

Antiviral Therapies: Turning Fatal Diseases into Manageable Chronic Conditions

When AIDS was initially discovered in the 1980s, it was a dreaded and deadly disease.

However, relentless efforts by scientists led to the rapid identification of the HIV virus responsible for AIDS, making the development of antiviral therapies against HIV possible.

In 1987, the FDA approved the first antiviral therapy, zidovudine (AZT), providing the first weapon against HIV. It inhibits the virus’s reverse transcriptase enzyme, preventing viral replication.

However, monotherapy quickly led to HIV developing resistance. In the mid-1990s, Professor David Ho and his team at the Aaron Diamond AIDS Research Center proposed the combination therapy, later known as the “cocktail.” They realized that providing patients with 3-4 different drugs simultaneously could outpace the virus’s mutation rate, effectively restraining it. The first protease inhibitor, saquinavir, was approved by the FDA in late 1995.

In 1996, Ho’s team found that patients on the cocktail saw a rapid reduction of HIV levels to undetectable levels. This breakthrough led to the standardization of the cocktail therapy the following year, resulting in a 47% reduction in AIDS-related deaths that year.

Today, with the emergence of various antiviral drug types, HIV-infected individuals can have life expectancies comparable to those without the virus as long as they adhere to their medication regimen. These drugs not only extend patients’ lifespans but also serve as preventive measures in high-risk populations.

Imatinib: Opening a New Chapter in Targeted Cancer Therapy

In 2001, imatinib (trade name: Gleevec) gained FDA approval for treating chronic myeloid leukemia (CML). It was one of the first precision therapies designed to target specific genetic mutations causing cancer, ushering in the era of targeted cancer treatment.

Initially, drug developers were cautious about targeting protein kinases due to their vital roles in normal physiological processes.

Scientists at Ciba-Geigy initiated a series of projects to find kinase inhibitors in the late 1980s. Through a series of design and modifications, imatinib exhibited high specificity in inhibiting the BCR-Abl protein, responsible for CML.

In clinical use, imatinib demonstrated remarkable efficacy, increasing CML patients’ 5-year survival rate from 30% to nearly 90%.

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