Curiosity-driven research explained: Laying the foundation for life-saving discoveries

It’s easy to associate success with speed in a world where modern conveniences mean we can, in the space of a minute, take a video call from halfway across the globe while ordering a new gadget with same-day shipping. (Both technologies stem from curiosity driven-research.)

Curiosity-driven research doesn’t promise quick results or profits. But it lays the foundation for discoveries that save lives.

Few of us see this work as it unfolds, but countless people experience its impact. More than 30 million Americans take statins to reduce their risk of cardiovascular disease. One in 8 have taken a GLP-1 drug. 40 million MRIs are performed in the U.S. each year, helping to diagnose everything from brain tumors to torn knee joints. And COVID-19 vaccines are estimated to have prevented over 14 million deaths.

Behind these enormous numbers are loved ones doing their best to navigate their health, creating ripple effects across their families, workplaces, and communities.

These impacts trace back decades — even centuries — with one generation of scientists after another building on discoveries unearthed by curiosity-driven research.

The discovery of cholesterol, for example, dates to 1815, just over 170 years before the approval of lovastatin as a treatment to reduce the risk of coronary artery disease. In between is a plodding timeline punctuated by a few early descriptions of arterial plaque buildup (atherosclerosis) and several incremental insights into the basic science of cholesterol synthesis and inhibition until finally, in 1978, scientists isolated the cholesterol inhibitor lovastatin. Nearly another decade passed before its approval as a drug.

Researchers at Novartis Institutes for BioMedical Research and Harvard University performed this kind of analysis for over 30 drugs, and found that the median time from scientific discovery to an approved therapy is more than three decades. You can explore their timelines documenting the path to treatments for infectious disease, cancer, neurological conditions, and more.

By contrast, the accelerated effort to bring COVID-19 vaccines to market might seem lightning fast. Only 16 months separate the first reported COVID-19 cases and wide availability of vaccines in the U.S. But decades of foundational, curiosity-driven research had laid the groundwork for this unprecedented effort — starting with a handful of research groups making their way towards the discovery of messenger RNA (mRNA for short) in the mid-twentieth century. Indeed, an earlier and ongoing motivation behind mRNA vaccines focuses on fighting cancer.

In 1984, researchers engineered biologically active mRNA in the laboratory for the first time, with the idea of using it to study how genes work. A few years later came the demonstration that human cells could absorb mRNA encapsulated in lipid droplets and produce proteins. And in 2005, scientists discovered how to modify synthetic mRNA to prevent the immune system from degrading it before it could deliver its message: the RNA transcript that could teach the cell how to fight off a viral attack.

Each of these milestones represents a critical step in the chain of discoveries that ultimately made rapid mRNA vaccine deployment possible.

Centuries-old science gave us the first observations of what would become entire fields like cell biology and quantum physics. Now, we live in an era of acceleration, with “use-inspired” impacts on human health motivating new discoveries. But this pattern, where basic research builds over many years towards sometimes unforeseeable transformative innovations, remains at its heart. It’s a feature, not a bug — and it requires resilient researchers who pursue long-term visions knowing their impacts may be felt only decades later.

Pursuing curiosity also means the path to innovation can be unpredictable, with scientific advances emerging from seemingly unrelated work, sometimes across entirely different fields.

Consider the fluorescent proteins used to visualize subcellular life. These proteins can be introduced into model organisms like fruit flies, zebrafish, and mice, where they “tag” the particular molecule researchers want to study so that it appears brightly in subsequent imaging. The origin of this transformative capability is Friday Harbor, off the Washington coastline, in the summer of 1961. Two Princeton scientists were brought to the harbor by a simple question about the jellyfish Aequorea victoria: why does it glow? In their studies analyzing the “squeezate” they collected from thousands of jellyfish, they discovered what later became known as Green Fluorescent Protein, or GFP.

Roughly a quarter century later, Martin Chalfie was sitting in a seminar when he learned about GFP from a visiting speaker. As a researcher focused on the transparent model organism, the worm C. elegans, Chalfie immediately realized the exciting potential of GFP to visualize the worm’s nervous system — and set about work to make this possible.

It’s a moment that forever changed biomedical research. Now GFP and other fluorescent proteins help us track the progression of disease, the activity of drugs against their targets, and gene expression.

Science is replete with similar stories.

Among them is the Wisconsin story behind warfarin, a blood thinner first marketed as a rat poison in the late 1940s and later identified as an effective treatment to prevent blood clotting in humans. In February 1933, Ed Carlson, a dairy farmer from Saint Croix County, drove 190 miles through a blizzard to UW–Madison seeking answers about his dead cow, one of many who had fallen victim to internal bleeding caused by sweet clover disease. Also in tow: a milk churn full of her blood and 100 pounds of the moldy hay she had been eating. A Saturday afternoon, Carlson had been looking for the state veterinarian, but wound up at the lab of Karl Paul Link in the Biochemistry building.

In Link’s telling, Carlson’s visit was the “direct catalytic hit” that spurred discovery into sweet clover disease. But the discoveries that arose from the decades of work started that afternoon far exceeded an explanation for sweet clover disease. Link’s colleague, also in the lab that fateful Saturday afternoon and mesmerized by the lack of clotting capacity in the blood that he rubbed through his fingers, sent Carlson home frustrated that it was with “promises [that] might come true in five, ten, fifteen years, maybe never.”

Karl Paul Link, professor of biochemistry and discoverer of warfarin, performs a laboratory procedure with fellow researcher Mark A. Stahmann. Photo: Gary Schulz. From the UW–Madison Collections

Their persistence over the next seven years to isolate the anticoagulant agent, dicumarol, and then another eight years finding a more appropriate derivative for clinical use, led to the patenting of warfarin as a rodenticide. Finally, after yet more work to refine dosing for human use, “cow poison” became not just “rat poison” but a lifesaving drug for humans, Coumadin, preventing potentially fatal blood clots.

However whimsically fated such stories seem, they also represent the payoffs of pure science cracked at, day after day, by researchers who are allowed to follow where their curiosity leads.

That freedom is as integral to modern science as in eras past — but arguably harder to come by.

Who pays?

Since World War II, the federal government has been one of the biggest funders of curiosity-driven science at research institutions across the country. This investment has produced countless health advances, kept the world safe from once-common diseases, and has trained the scientific workforce that can respond to emerging threats.

It has also generated profound economic growth. In Wisconsin alone, funding from the National Institutes of Health supported more than 6,700 jobs and $1.38 billion in economic activity in 2024, according to United for Medical Research. Nationally, that number is over 94 billion, translating to $2.56 of economic activity for every $1 of research funding.

But it’s not just federal support that makes this work possible. The total share of basic research footed by federal funders has decreased relative to increases from the business and philanthropy sectors over the last several decades, going from 70% of total funding for basic science in the 1960s down to 51% in recent years.

Broad, blended financial support for curiosity-driven research is more important now than ever. Even before proposed cuts to federal funding threw the world of basic research into damaging uncertainty in 2024, many have been concerned about funding trends, including that decline in the federal share and a tendency to favor incremental pre-proven advances instead of bold questions into the unknown.

Curiosity lays the essential foundation for successful applied research and translation to products and profits. A shaken foundation compromises the integrity of this entire ecosystem. So without continued investment in curiosity-driven science, the impact of those downstream effects will also begin to shrink.

The Morgridge Institute takes a distinctive approach to curiosity-driven research: Fearless Science. This is our commitment to taking the advisable risks that will advance new knowledge, and this ethos is rooted in our origin story. Jamie Thomson’s basic research into embryo development in non-human primates led to his pioneering work in stem cells, leading to the founding of the Morgridge Institute in 2006 and supporting Wisconsin’s growth into a national leader in regenerative biology.

Now we are home to 20 investigators who are pursuing new frontiers in biology, alongside new groundbreaking technologies and new understandings of the deep connections between science and society.

Some of the questions we’re following take us:

Without sustained support for curiosity-driven research, the engine behind life-saving discoveries will falter and talented researchers may leave the field. Investing in curiosity-driven research builds the foundation for the breakthroughs of tomorrow.

On the most fundamental of levels, this support speaks to a human need to know more about why we’re here and where we’re going.

Our only limit is our curiosity.