Blog 24: Fighting Rare Diseases Through Forced Evolution

Picture this: you're one of only 300 people in the world with a disease so rare that no treatments exist. And it's not because doctors don't care about getting you better, it's because our evolution hasn't had enough time to offer us a solution. Life itself doesn't have an answer to make you better. That's where the concept of forced evolution comes in. 

What are Rare Diseases?

A rare disease is defined as a condition that affects less than 200,000 people in the United States. When added up, there are more than 7,000 rare diseases with over 30 million Americans being affected.  That's close to 1 in 11 people. Despite attempts to treat these illnesses, only ~5% of rare diseases have an FDA-approved treatment. With such a low rate of treated diseases, most patients, once diagnosed, have to deal with years of misdiagnoses, limited options, and lots of uncertainty. 

Luckily, forced evolution has given researchers and scientists a chance to give these people clarity. 

What Is Forced Evolution?

Forced evolution is exactly what it sounds like: pushing biological systems to evolve on demand, rather than waiting thousands or millions of years for natural selection to do the work. In the lab, scientists introduce pressure that causes mutations in cells or proteins. These mutations are random, but some of them just might improve the function of a protein, or give a cell the ability to survive a disease-related condition. Researchers then select the best performers and repeat the process. Over time, they evolve a new biological function that nature hasn't yet had time to produce.

This process is also called directed evolution, and it’s been used to build enzymes that are more stable, proteins that bind better, and even molecules that can reverse the effects of genetic diseases. In fact, the Nobel Prize in Chemistry in 2018 was awarded for advances in this very field. Forced evolution is quickly becoming one of the most powerful tools in the synthetic biologist’s toolkit.

How Forced Evolution Helps Treat Rare Diseases

When a rare disease is caused by a faulty or missing protein, one solution is to engineer a better version of that protein. But designing that protein from scratch is incredibly difficult. Instead, scientists can evolve the protein in the lab. They might start with a version that works poorly, then subject it to rounds of mutation and selection until it works well enough to serve as a treatment. This approach has already shown promise in diseases like cystic fibrosis and certain metabolic disorders.

In some cases, researchers evolve entirely new enzymes. Others are working on evolving gene-editing tools, like CRISPR enzymes, to be more precise and safer for use in patients with ultra-rare mutations. This ability to "train" biology to do what we need is a game-changer for people whose diseases have long been ignored by traditional pharmaceutical models.

Why SynBio + Forced Evolution Is So Powerful

Synthetic biology takes forced evolution to the next level. Instead of relying solely on randomness, SynBio lets scientists steer evolution more intelligently. For example, they can design gene circuits that simulate the pressures of a disease environment, forcing cells to adapt in a way that mimics what patients actually experience. They can use DNA sequencing and AI to track which mutations are most helpful. And thanks to advances in automation, entire rounds of mutation, growth, and selection can now happen in just days.

This blend of evolution and engineering means we’re no longer limited to what nature has created. We can design new proteins, custom enzymes, and even reprogrammed cells that never existed before.

A Future with Fewer Untreatable Disease:

If researchers can define what a "better" outcome looks like (for example, more enzyme activity or less buildup of a harmful chemical), they can evolve their way to a solution. That makes this method especially useful for rare diseases, where traditional research often stalls due to a lack of funding, data, or patients.

As SynBio and forced evolution continue to converge, we may one day be able to custom-evolve treatments for individual patients, based on their unique biology. What used to take a million years could become routine in the next generation of medicine.

Thanks for listening, can't wait to be back next week!

--- Aidan Kincaid