The Shape of Things to Come: A Columbia Biophysicist Tells the Story of His Life’s Work

Hashim M. Al-Hashimi, PhD, has spent his career challenging one of biology’s most basic assumptions: that the molecules inside our bodies are fixed and unchanging. By showing that DNA and RNA are constantly moving, he has helped reshape how scientists think about disease, from HIV to cancer, and how new treatments might be designed.

For Dr. Al-Hashimi, the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics and associate dean for biomedical graduate education, the path to that discovery was anything but straight. Growing up across multiple countries during times of conflict, he learned early that nothing stays still for long. That perspective would later shape how he approached science—and what he chose to question in his lab.

As a newly elected member of the prestigious National Academy of Sciences, Dr. Al-Hashimi tells his story.

I’ve lived many lives before I ever ran a lab. I think all that movement shaped how I see the world. Nothing felt fixed. And that idea of things always being in motion ended up guiding my life’s work.

I was born in Beirut, Lebanon, just as the civil war began. My family moved often—first to Greece, then Italy, then Jordan. I went to high school in Wales to escape another war. By the time I finished my education, I had studied in London and then come to the United States for my PhD.

When I arrived in the U.S. for graduate school, I began studying something called nuclear magnetic resonance (NMR) spectroscopy. It’s like magnetic resonance imaging (MRI), but instead of imaging organs, it lets us study molecules—like DNA and RNA—at the atomic level.

At the time, most scientists believed these molecules were stable and fixed, like tiny sculptures. You could take a picture of them and understand how they worked.

But that didn’t sit right with me. Life isn’t static. We move. Our cells move. Why wouldn’t the molecules inside us move too?

So, I joined a team that was asking a controversial question: What if these molecules aren’t rigid at all? What if they are constantly shifting?

Back then, suggesting that molecules moved was almost heretical. There were already beautiful images of proteins and DNA. Scientists trusted those images. They saw structure and assumed stability. But the data we were seeing suggested something different.

The challenge is NMR doesn't produce a "movie," just numbers that have to be interpreted. And those numbers can be debated. Some scientists argued that the data could still fit a static model. I spent years showing that the only explanation that truly fit the data was movement—constant, meaningful motion.

It took a long time for the field to accept that idea, but the shift has begun.

Later in my career, I turned to studying RNA. At the time, RNA was thought to be floppy and unstructured—almost like spaghetti. That made it a perfect test case. If my methods worked anywhere, they should work there.

One night, after struggling with the data, I tried something simple. Instead of modeling RNA as complex shapes, I treated parts of it like simple building blocks—almost like Lego pieces. Each piece was stable, but the connections between them could move.

Suddenly, everything made sense.

For the first time, I could clearly see how one part of the RNA moved relative to another. The motion was huge—far more than anyone expected. It was like watching something come alive.

That discovery changed my career.

Here’s why it mattered so much.

Many diseases depend on how molecules interact inside your body. For a long time, we thought viruses, cancer cells, and bacteria had a specific molecular shape, like a lock. So, in order to treat a disease, we’d develop a drug to fit that shape, like a key. But what we’ve learned is this: the lock is constantly changing shape. If you look only at one snapshot, you might miss the real target for a drug. But if you understand all the shapes a molecule can take, you can design better treatments—ones that fit more precisely and work more effectively.

In HIV, for example, there is a piece of RNA that the virus needs to function. Scientists had already seen that different drugs could bind to this RNA—but each drug seemed to change the RNA’s shape in a different way. That was confusing.

But when we looked at the RNA in motion, the answer became clear. The RNA was already sampling all those shapes on its own. The drug wasn’t forcing the change. The drug was simply binding when the RNA happened to be in the right shape.

This means drugs don’t just create a fit—they find the fit. And if we can map all the possible shapes, we can design drugs that bind more precisely. For patients, this means more targeted treatments that carry fewer side effects and offer better chances of success.

We used these ideas to build technology that can predict which drugs will bind to RNA—and which won’t. That led to the creation of a company focused on developing new therapies.

Today, we can screen trillions of potential compounds on a computer before ever making a drug in the lab, and that speeds up discovery in a major way. It also opens the door to treating diseases we couldn’t target before—especially those involving RNA, which has traditionally been very difficult to treat with drugs.

We’re also studying DNA—the molecule that carries your genetic code. You’ve probably seen the image of DNA as a perfect double helix. It looks stable and protected. But we’ve discovered that even DNA is constantly shifting.

Sometimes, individual pieces briefly flip out of the structure. When that happens, they become exposed—and vulnerable to damage. That matters because damage to DNA is what leads to mutations, and mutations are what can lead to cancer.

In fact, we’ve found that certain types of DNA movement are linked to the same mutation patterns seen in lung cancer, especially in people who smoke. This link creates a direct connection from molecular motion to DNA damage and cancer risk.

One of the most exciting possibilities of this work is using this knowledge to identify risk earlier. If we can map how a person’s DNA tends to move, we may be able to see where it’s more vulnerable to damage. That could lead to early warning markers for cancer risk, personalized prevention strategies, and better guidance on lifestyle risks.

For patients, this research represents a shift in how we understand disease. We are moving from static snapshots to dynamic systems, which means better drug design, new treatment strategies, and earlier detection of disease. It also means we can begin to answer deeper questions—like why certain people are more vulnerable than others.

When I think about my journey—from moving across countries as a child to studying molecules in motion—it all connects.

What I’ve learned is that change isn’t a flaw in biology. It’s a feature. Molecules move because life depends on flexibility. That flexibility allows your body to function, adapt, and survive. But it also creates vulnerability. Disease often happens when that balance between flexibility and vulnerability is disrupted.

Even now, after decades of work, I’m still studying the same RNA molecule I started with years ago. And it still surprises me. That’s the nature of science. The deeper you look, the more complexity you find. Within that complexity, there is also opportunity. Every new movement we uncover is a chance to understand disease better—and to help patients in ways we couldn’t before.

That’s what drives me. Because at the end of the day, this isn’t just about molecules. It’s about people. And the possibility of giving them better outcomes, longer lives, and more control over their health.

This as-told-to story is based on a conversation with Hashim M. Al-Hashimi, PhD, and has been edited for length and clarity.