Bizarre trials that changed the game.

Compliance, endpoints, and recruitment funnels. These are the things we think about when it comes to clinical trials. Very strategic, very regulated, very on the nose. But every now and then, medicine zigs when you expect a zag, and those zags can fundamentally change everything.

Scurvy. Starvation. The history of medicine is filled with strange circumstances and determined people who pushed the limits of what we knew – sometimes by design, sometimes by necessity. And while clinical trials have come a long way in ethics and methodology, these unexpected origins prove that science isn’t always a linear progression. Sometimes it’s weird and unexpectedly brilliant.

Let’s explore a couple of strange-but-true studies that helped shape the modern landscape of clinical research.

Sailors and citrus: The scurvy study.

In 1747, scurvy was hitting sailors fast, and no one really knew what to do about it. On board the HMS Salisbury, British naval surgeon James Lind wanted to solve this deadly problem.

So Lind did something surprisingly modern, he ran a trial. He divided 12 sailors into six groups and gave each a different treatment:

1. One quart of cider daily
   • Results: Mild improvement
2. Elixir of vitriol (diluted sulfuric acid): 25 drops, three times a day
   • Results: No significant improvement
3. Two spoonfuls of vinegar three times a day
   • Results: No improvement
4. A half pint of seawater daily
   • Results: Probably made them worse
5. A mix of garlic, mustard seed, radish root, balsam of Peru, and myrrh taken with barley water
   • Results: Minimal effect
6. Daily intake of two oranges and one lemon
   • Results: Rapid and dramatic recovery, with one sailor returning to duty in just six days

Lind didn’t know why it worked (vitamin C wouldn’t be discovered for another 180 years), but he recorded the results and pushed for change. It took a few more decades before the British Navy fully adopted citrus as a scurvy preventative, but when they did, it saved thousands of lives.

It wasn’t perfect science. But it was structured observation with real-world impact. And in many ways, it laid the groundwork for how we think about clinical trials today.

Minnesota and rations: The starvation study.

In the middle of World War II, a team at the University of Minnesota, led by Dr. Ancel Keys, set out to answer a grim but essential question: What happens to the human body when food runs out, and how do you bring someone back from the edge of malnourishment?

A total of 36 conscientious objectors (people who refused to fight or serve in the military because of moral, ethical, or religious beliefs against killing or war) volunteered for the job as an alternative to combat. For six months, they lived on about 1,500 calories a day instead of their usual of roughly 3,200 calories a day and walked 22 miles a week – not as punishment, but as preparation. With millions across Europe facing famine, the US needed real data to guide postwar relief.

The results were intense. Participants lost weight, energy, and, at times, hope. But their sacrifice shaped how the world approaches recovery from starvation. The data they generated still informs nutrition guidelines, humanitarian aid, and even eating disorder treatment today.

It wasn’t flashy. It wasn’t comfortable. But it was one of the first times research balanced scientific rigor with human empathy – a model for what ethical study design could look like long before “informed consent” became standard.

Unusual origins, essential lessons.

Clinical trials today are more regulated, inclusive, and transparent than ever – and for good reason. From maritime medicine to studies born out of hardships, each strange chapter in medical history has added to our understanding of how to test, protect, and improve human health.

They remind us that:

• Breakthroughs often start with curiosity, not certainty
• Even missteps can spark reform and progress
• Visibility and public trust have always been the foundation of good science

So the next time you’re designing a complex protocol, easing patient concerns, or looking for new ways to boost enrollment, don’t forget: Clinical research has always evolved through curiosity – sometimes in surprising ways. And that curiosity, paired with integrity and innovation, is what drives the field forward.

Need a partner who brings curiosity, integrity, and innovation to your trial recruitment? Let’s connect!