Swimming upstream

While I love my backyard koi pond, I don’t know much about fish in the wild. Knowing I needed to write this column, I did what many of us do when venturing into unfamiliar waters: I turned to the internet and began researching.

I learned that it isn’t just salmon that swim upstream. Sturgeon, striped bass and even the tiny freshwater zebrafish are known to push against the current. When zebrafish — frequently used in scientific research because of their genetic similarity to humans — encounter strong currents or turbulent waters, they tend to swim in schools. This collective behavior helps them conserve energy, avoid predators, and even reduce stress, as each individual fish is steadied by the rhythm of the group.

In short, for zebrafish, cooperation is an essential survival strategy. For many reasons, that insight feels deeply relevant to this issue’s cover story.

Rare and ultra-rare disease patients have long been forced to struggle upstream. Prior to the completion of the Human Genome Project in 2003, researchers lacked access to the full human genome. Without that foundational knowledge, accurately diagnosing the genetic causes of disease — let alone treating them — was often impossible.

Advances in genetics and the emergence of gene therapies represented a sea change for rare disease. Many of these disorders stem from single-gene mutations, making them well-suited for gene correction. Unlike traditional medicines that manage symptoms, gene therapies hold the promise of addressing disease at its root, offering durable treatments and, in some cases, potential cures.

But another challenge surfaced. The economics of developing drugs for very small patient populations were rarely enough to entice for-profit pharmaceutical companies. Layer on the logistical complexity, manufacturing hurdles, and high costs associated with cell and gene therapies, and the waters became even more difficult to navigate.

So patients and their families did what they had to do to survive. They mobilized. They formed advocacy organizations, collected data, hired researchers, launched clinical trials, and in some cases, even founded their own biotech companies. They raised funds through bake sales and crowdfunding platforms, driven by urgency and hope, all in pursuit of treatments for their loved ones.

By joining forces, these patients and families have created a powerful, impossible-to-ignore, advocacy-driven movement.

Today, there are signs that the current may be shifting. Regulators, through openness to novel trial designs, new guidance, and alternative approval pathways, are signaling flexibility in bringing therapies to small patient populations. At the same time, drug developers in the cell and gene therapy space are beginning to find efficiencies — reducing costs and expanding access.

Which raises an important question: Can industry find sustainable ways to work with patient advocacy organizations — models that both support innovation and help turn the tide for rare disease treatment?

As I wrapped up my admittedly surface-level fish research this month, I couldn’t help but imagine what it would feel like to receive a rare disease diagnosis for a child or family member — and suddenly be thrust into a world you know nothing about, with the stakes being someone you love. No one should be forced into a sink-or-swim situation when the outcome matters that much.