How Clinical Trials Changed Medicine

Clinical trials have been a cornerstone of modern medicine. From exploring how diet affects health outcomes to discovering new diseases and treatments, and from managing everyday illnesses to testing cutting-edge technologies, clinical trials have continually advanced healthcare and improved lives.

 

A Brief History of Clinical Trials

Clinical trials date back as far as 500 BCE, with one of the earliest documented examples found in the biblical ‘Book of Daniel.’ King Nebuchadnezzar, a military leader—not a physician—ordered his people to consume only meat and wine, believing it would keep them in peak condition. However, a group of young men preferred a diet of vegetables and water. The king allowed them to follow their preferred diet for ten days. At the end of the experiment, the vegetarians appeared healthier than the meat-eaters, prompting the king to permit the vegetarian diet. This marks one of the earliest recorded instances of a human experiment influencing public health policy.

 

The first official clinical study occurred in 1747 when British physician James Lind conducted an experiment aboard a ship plagued by scurvy. Lind divided twelve crewmen into groups and administered different treatments. The group treated with oranges and limes recovered within six days, leading to the British government mandating citrus in sailors’ diets. Lind’s work is commemorated annually on May 20 as International Clinical Trials Day.

 

These stories illustrate how clinical trials have shaped healthcare—even centuries ago. This article explores what defines a clinical trial and how these studies have transformed medicine.

 

What Are Clinical Trials?

To appreciate their impact, we must first understand what clinical trials are. Clinical research investigates health and illness in people, aiming to discover better ways to treat or prevent diseases. There are two main types: observational studies and interventional studies.

Observational studies monitor participants in natural settings, collecting data over time to identify patterns or potential treatments. Interventional studies test new treatments—such as drugs, diets, or medical devices—to evaluate their safety and effectiveness.

 

Clinical trials typically progress through four phases:

Phase I: Tests a new treatment in a small group (20–80 people) to assess safety and identify side effects.

Phase II: Expands to a larger group (100–300 people) to evaluate effectiveness and further examine safety.

Phase III: Involves a large group (1,000–3,000 people) to confirm effectiveness, monitor side effects, and compare with existing treatments.

Phase IV: Conducted after FDA approval, this phase monitors long-term safety and effectiveness in the general population.

 

Ethics and Regulation: A Necessary Evolution

While clinical trials have long contributed to medical progress, their ethical history is complex. The Hippocratic Oath, emphasizing ‘do no harm,’ has guided physicians for centuries. Yet, many early human experiments ignored this principle.

 

The atrocities committed during World War II, particularly by Nazi doctors, led to the creation of the Nuremberg Code in 1947—the first international ethical guideline for human research. It emphasized informed, voluntary consent and outlined ten principles to protect participants.

 

In the U.S., the Institutional Review Board (IRB) oversees all clinical trials to ensure ethical standards and participant safety. This system emerged in response to unethical studies like the Tuskegee Syphilis Study and Willowbrook Hepatitis Experiments.

 

Clinical Trials in the Last 50 Years

With ethical safeguards in place, clinical trials have flourished, yielding groundbreaking discoveries. Here are two transformative examples:

 

Vaccine Development: The MMR Vaccine

Measles, one of the most contagious diseases, has plagued humanity for centuries. Despite improvements in nutrition and sanitation, measles caused over 2 million deaths annually in the 20th century.

 

In 1954, doctors at Boston Children’s Hospital isolated the measles virus from a student named David Edmonston. This led to the development of the first measles vaccine, tested between 1958 and 1960. By 1961, it was found to be 100% effective and was licensed in 1963.

 

Dr. Maurice Hilleman improved the vaccine in 1968, reducing side effects. In 1971, he combined vaccines for measles, mumps, and rubella into the MMR vaccine, later expanded to MMRV with varicella in 2005.

 

Thanks to widespread vaccination, measles rates have plummeted. The World Health Organization recommends two doses—at 12–15 months and 4–6 years. Maintaining high immunization rates is crucial to prevent outbreaks.

 

Between 2000 and 2023, the MMR/MMRV vaccines are estimated to have prevented over 60 million deaths worldwide.

 

Gene Therapies: CRISPR and Immunotherapy

Cell and gene therapies treat diseases by transferring cells or genetic material into patients. The concept began in the 1960s, but the first successful gene therapy occurred in 1990.

 

By the 2000s, genome editing tools like ZFNs and TALENs were used to treat HIV and cancer. Progress accelerated with the discovery of CRISPR/Cas9 in 2012.

 

CRISPR allows precise, affordable gene editing using a guide RNA and an endonuclease. Its simplicity has revolutionized gene therapy.

 

In 2016, the first ex vivo CRISPR T cell therapy trial began. Since then, CRISPR has enabled therapies like CAR T cell, TCR cell, and NK cell therapies.

 

In 2020, Emmanuelle Charpentier and Jennifer Doudna won the Nobel Prize in Chemistry for CRISPR. In 2023, the FDA approved Casgevy for sickle cell disease.

 

In 2025, researchers developed a personalized CRISPR therapy for CPS1 deficiency—a rare and fatal condition.

 

Bottom Line

Clinical trials have transformed medicine—from ancient experiments to modern gene editing. While their ethical history is fraught, today’s trials prioritize safety, informed consent, and patient autonomy.

 

We’ve seen how trials led to life-saving vaccines and revolutionary therapies like CRISPR. As science advances, ethical frameworks will evolve to protect participants while enabling discovery.

 

If you’re curious about participating in a clinical trial, talk to your healthcare provider or visit clinicaltrials.gov to explore opportunities based on your condition, location, and eligibility.