The Radical Openness of Science and Innovation
Embracing Uncertainty to Drive Discovery
What If Everything We Know Is Incomplete?
Imagine for a moment that your brain is hardwired to resist the very uncertainty that breakthrough science requires. That the organ we rely on for discovery is actually built to avoid the unknown, preferring familiar patterns and predictable pathways. This isn't science fiction—it's what neuroscience reveals about our innate cognitive biases that make genuine innovation so difficult 1 .
Yet against these biological odds, science and innovation continue to advance at an accelerating pace. How? Through what leading researchers and policymakers call radical openness—a conscious, deliberate embrace of uncertainty, collaboration, and exploration beyond the boundaries of established knowledge. This mindset shift is transforming how we approach everything from drug development to climate change, creating new models for discovery that acknowledge the inherent unpredictability of research while dramatically accelerating its impact 2 .
Cognitive Barriers
Our brains naturally resist uncertainty, creating inherent barriers to innovative thinking that must be consciously overcome.
Accelerated Discovery
Radical openness creates pathways for breakthrough discoveries that traditional approaches might miss or delay for decades.
The Science of Openness: Why Our Brains Resist Innovation
What Is Radical Openness?
Radical openness represents a fundamental shift in how we approach knowledge creation and innovation. It's not merely about sharing research papers or collaborating across disciplines—though both are important. True radical openness involves:
- An attitude of consciousness that prepares us to think differently and act accordingly 1
- Acknowledging and embracing uncertainty rather than avoiding it 2
- Willingness to challenge well-established patterns and abandon them when necessary 1
- Creating systems that thrive on the cusp of uncertainty where breakthrough discoveries occur 2
The Innovation Paradox
This creates what we might call the innovation paradox: our brains are simultaneously our greatest assets for scientific discovery and our biggest obstacles to breakthrough thinking. Novelty, by definition, concerns something that has not existed before, which means it cannot be fully predicted from past experiences. As one researcher notes, "You can hardly predict anything new if you have never seen what leads to such novelties" 1 .
"You can hardly predict anything new if you have never seen what leads to such novelties" 1 .
The solution lies in consciously adopting what theLivingCore describes as an "epistemic attitude of radical openness"—a deliberate mindset that must be cultivated over time through developing essential cognitive skills like asking relevant questions, close observation, deep understanding, and sensitivity to potential 1 .
The Policy Perspective: Europe's Bet on Open Science
The Three Opens
The importance of radical openness isn't just theoretical—it's being embedded into science policy at the highest levels. In 2015, European Commissioner for Research, Science and Innovation Carlos Moedas proposed three strategic priorities for Europe:
Open Innovation
Accelerating commercialization of research through novel funding and investment models 2 .
Openness to the World
Addressing major social, health and environmental problems through international scientific cooperation 2 .
Beyond Commercialization
While these priorities are laudable, some researchers argue that true radical openness goes beyond commercialization and problem-solving. As one analysis notes, "science, especially basic science, is in itself more radically open toward the future when it is free to explore the vast domain of the yet unknown" 2 .
This perspective highlights how basic research—often criticized for its lack of immediate practical application—represents one of the most profound forms of openness: exploration without predetermined outcomes. The most transformative breakthroughs frequently emerge from this curiosity-driven space, often decades before their practical applications become clear.
| Aspect | Traditional Science | Radically Open Science |
|---|---|---|
| Primary Driver | Incremental advances within established paradigms | Exploration of fundamentally new questions and approaches |
| Uncertainty | Treated as a problem to eliminate | Embraced as a source of potential discovery |
| Collaboration | Limited within disciplines and institutions | Extensive across disciplines, sectors, and geographies |
| Data Sharing | After publication, if at all | Throughout research process whenever possible |
| Failure | Minimized or hidden | Recognized as valuable learning opportunity |
Principles for Radical Innovation: From Theory to Practice
The Five Principles
How does radical openness translate into practical innovation? At Regeneron, a biopharmaceutical company known for its breakthrough discoveries, President and Chief Scientific Officer George D. Yancopoulos has developed five core principles for radical innovation 4 :
1. Challenge everything
Take a beginner's mindset and challenge all assumptions 4 .
2. Be willing to risk failure
Understand that great advancements require risking failure every day 4 .
3. Identify fundamental truths
Simplify complex truths to their core essence 4 .
4. Identify limiting bottlenecks
Understand what prevents progress 4 .
5. Create simple solutions
Use fundamental truths to overcome bottlenecks and create breakthrough platforms 4 .
The VelocImmune Breakthrough
These principles came to life in Regeneron's development of the VelocImmune mouse, which overcame a critical bottleneck in drug development. For decades, scientists had struggled to produce effective therapeutic antibodies from mice because their immune systems recognize human pathogens differently than humans do. Where others saw limitations, Regeneron asked a bold question: Could mice be engineered to carry human immune genes? 4
The result was a remarkable research tool that produces precisely humanized antibodies—now responsible for more FDA-approved medicines than any other platform in biotech history. This breakthrough required challenging fundamental dogmas, persisting through more than a decade of development, and creating a simple solution to a complex problem 4 .
In-Depth Look: The VelocImmune Experiment
Methodology: Step-by-Step Development
The creation of the VelocImmune mouse represents a classic example of radical openness in action. The process unfolded over many years through these key stages:
Identifying the Bottleneck
Researchers recognized that the existing method of producing monoclonal antibodies had significant limitations—they were time-consuming to develop and often triggered immune rejection in humans because they contained nonhuman components 4 .
Challenging Assumptions
Where the scientific consensus held that antibodies could only be derived from animals and those foreign proteins would always face immune rejection, the Regeneron team asked whether this limitation could be overcome through genetic engineering 4 .
Developing Novel Technology
Despite the technology to achieve this not existing at the time, the team spent over a decade developing methods to replace mouse immune system genes with their human counterparts, creating a mouse with a humanized immune system 4 .
Validation and Iteration
The resulting VelocImmune mouse was rigorously tested to ensure it could produce precisely targeted human antibodies that would be effective therapeutics without triggering immune rejection 4 .
Results and Impact
The VelocImmune platform has transformed drug development, leading to multiple FDA-approved medicines for conditions ranging from cardiovascular disease to cancer. The platform's success demonstrates how overcoming a fundamental bottleneck can create ripple effects across multiple therapeutic areas 4 .
| Parameter | Traditional Monoclonal Antibodies | VelocImmune-derived Antibodies |
|---|---|---|
| Human Compatibility | Often limited due to non-human components | High due to fully human antibodies |
| Development Timeline | Typically several years | Significantly accelerated |
| Success Rate | Low due to immune rejection issues | Substantially higher |
| Platform Potential | Limited to specific targets | Broadly applicable across diseases |
| Commercial Impact | Individual products | Multiple blockbuster medicines |
The Scientist's Toolkit: Essential Elements for Open Science
Research Reagent Solutions
What does it take to practice radically open science? Beyond mindset and policy support, specific tools and approaches enable this way of working:
| Tool/Method | Function | Role in Open Science |
|---|---|---|
| Open Access Publishing | Makes research immediately available without constraints | Democratizes knowledge access beyond wealthy institutions 2 |
| Preprint Servers | Enables rapid sharing of unreviewed research | Accelerates feedback and collaboration before formal publication 6 |
| Data Deposit Systems | Provides detailed materials, methods, and raw data | Enables validation, reproduction, and secondary analysis 6 |
| Genetic Engineering Tools | Allows precise modification of biological systems | Enables creation of novel research models like VelocImmune 4 |
| AI and Machine Learning | Processes massive datasets to identify patterns | Helps generate hypotheses and identify connections across disciplines 7 |
The Human-AI Collaboration
Emerging technologies, particularly artificial intelligence, are creating new possibilities for open science. As one analysis notes, "human-AI collaboration has enormous potential to enhance scientific creativity by freeing researchers from the constraints of routine processes, allowing them to concentrate on exploring new frontiers of knowledge" 7 .
Initiatives like Stanford University's Virtual Laboratory concept demonstrate this potential, with AI agents trained in various disciplines working alongside human researchers to break down complex problems into manageable tasks. This creates a novel model of systemic research that challenges conventional paradigms of knowledge generation 7 .
Human-AI Collaboration
AI systems can process vast datasets to identify patterns and connections that might elude human researchers, accelerating discovery while humans focus on creative problem-solving and hypothesis generation 7 .
Conclusion: Embracing the Unknown
The journey toward radical openness in science and innovation represents both a return to fundamental scientific values and a dramatic break from established practices.
It acknowledges what the most creative scientists have always known: that true discovery happens at the frontier of the unknown, where uncertainty is highest and predictability lowest.
"Short of a time machine, science is the most powerful tool that humanity has invented to bring the future into the present" 2 .
As European researchers noted, "Short of a time machine, science is the most powerful tool that humanity has invented to bring the future into the present" 2 . This remarkable capacity depends not on avoiding uncertainty, but on embracing it—on developing what François Jacob called "night science," the messy, iterative, often frustrating process of exploration that occurs before the clear light of "day science" reveals a breakthrough 2 .
The challenge now lies in building systems—from education to funding to publication—that recognize and support this reality. That means valuing incremental contributions alongside dramatic breakthroughs, supporting high-risk exploration without guaranteed outcomes, and creating collaborative networks that span disciplines and sectors. As we look toward increasingly complex global challenges, from climate change to pandemics, this radical openness may be our most essential tool for creating a better future.
Science thrives on the cusp of uncertainty—the rare moments of intense creativity when completely new perspectives and visions open up and lead to new discoveries and insights 2 .
Our task is to create the conditions where those moments can flourish.