In medicine, can first principles supersede evidence-based medicine?

I don't think so. They are more like partners than substitutes.

Let me use an analogy to help you understand:

Evidence-based medicine is like "cooking by following a recipe."

This recipe isn't something someone just came up with on a whim; it's the "optimal solution" summarized by thousands of chefs after countless trials and improvements. For example, a "braised pork recipe" tells you what kind of meat to use, how big to cut it, how much sugar and soy sauce to add, and how long to stew it. If you follow it, you'll most likely make a delicious plate of braised pork.

In medicine, this "recipe" is large-scale clinical trial data. Most of the medications doctors prescribe and surgeries they recommend have been validated on many people and proven safe and effective. This is to ensure the stability and reliability of treatment, as lives are at stake, and you can't just be used as a guinea pig.

First principles thinking is like "understanding the chemical and physical principles of cooking."

It doesn't care about specific recipes but asks the most fundamental questions: Why does meat change color at high temperatures (Maillard reaction)? Why does sugar caramelize? Why does baking soda make dough fluffy?

Once you grasp these underlying principles, you're no longer just a chef who follows recipes; you become a master chef who can create new dishes. You know you can combine techniques from recipe A with ingredients from recipe B, and there might be a pleasant surprise.

In medicine, first principles thinking means exploring the most fundamental logic of life and disease. For example, why does a certain cancer cell proliferate indefinitely? What is its energy source? Is there a molecule that can precisely cut off its energy supply without harming normal cells? All new drug development and new therapy exploration originate from this way of thinking.

So, why can't "understanding the principles" directly replace "following a recipe"?

It's simple: the human body is incredibly complex!

Based on chemical principles, you might think ingredients A and B would taste great together, but in practice, the dish might taste strange or even be toxic. That's because you didn't account for dozens of other unexpected byproducts they might produce at high temperatures.

Similarly, scientists might design a new drug based on first principles, theoretically capable of "starving" cancer cells. However, when used in humans, it might cause various unexpected side effects, or the drug might be metabolized before it even reaches the cancer cells, or even cause severe damage to the liver and kidneys.

So, the process is as follows:

1. Scientists use first principles to think, propose an innovative idea, and develop a new drug (like inventing a completely new dish).
2. Then, the new drug must be validated using evidence-based medicine methods through rigorous, large-scale clinical trials (repeatedly testing this new dish) to see if it is effective and safe.
3. Only when it is proven effective and safe can it be written into a new "recipe," become a standard treatment plan, and be promoted for public use.

To summarize: First principles are responsible for innovation and breakthroughs, serving as the engine of medical development, telling us "why"; evidence-based medicine is responsible for validation and safeguarding, serving as the cornerstone of medical safety, telling us "what" and "how." Neither can be dispensed with; one guides the direction, the other ensures steady progress.