Gap Map

Gap Map
Fundamental Development Gap Map v1.0
Welcome! This is a new web portal by the team at
Convergent Research
that we built out with the help of scientists and researchers in our ecosystem to explore the landscape of R&D gaps holding back science and the bridge-scale
fundamental development
efforts that might allow humanity to solve them. To illustrate this, we’ve created a dataset showing the relationships between the following:
R&D Gaps:
we’ve focused on “fundamental development” gaps that may need coordinated research programs to solve by building a mid-sized piece of infrastructure.
Foundational Capabilities:
tools, technologies, data (mid-sized science infrastructure) that could fill the related R&D gap
Resources:
for each foundational capability, the initiatives and organizations working toward it; relevant research papers, roadmaps, and technology seeds; and ideas (proposals, whitepapers, essays, etc.) illustrating the capability.
This is just v1.0 of the map, so it isn’t comprehensive - at all! We’re putting it out to help you get an intuition for how folks in our ecosystem think about the scientific landscape, spark discussion, and to get your constructive and critical feedback.
You can read more about the “how” and “why” behind it
here
, learn more about the contents and how to use it
here
, and suggest contributions to it
here
. Have other questions or comments? Reach out to us at
gapmap@convergentresearch.org
Filter by Field
R&D Gaps
Capabilities
Resources
Loading
grid
view
Most Brain Circuitry is Still Invisible
Neuroscience
Understanding the complete wiring of the brain at single–cell resolution, along with detailed molecular annotations, is critical for revealing how neural circuits support learning, memory, and behavior. Current technologies are prohibitively expensive and lack scalability, limiting our ability to link molecular composition with circuit connectivity and to understand the alterations present in brain disorders. This gap fundamentally makes diagnosis, treatment, and prevention of many brain disorders more difficult. Beyond the biomedical applications, maps of brain circuitry could play a fundamental role in grounding principles of safety for brain-like AI systems.

Initiatives like the NIH BRAIN Initiative’s transformative projects (the BRAIN Initiative Cell Atlas Network (BICAN), the BRAIN Initiative Connectivity Across Scales (BRAIN CONNECTS) Network, and the Armamentarium for Precision Brain Cell Access) represent important efforts to illuminate foundational principles governing the ci...
Neuroscience
Fundamental Biomolecular Actors in Cells Remain Largely Invisible
Cellular and Molecular Biology
Many of the fundamental actors in cells—proteins, lipids, and metabolites—are still mostly invisible to us, especially when considering their extensive multiplexity, diversity, cell-to-cell heterogeneity, and temporal variation. Without scalable, cost-effective technologies to capture these molecular details, our comprehensive analysis of complex biological systems remains limited.
Cellular and Molecular Biology
Current “Model Systems” for Brain Function are Not Representative of the Real Human Brain
Neuroscience
Current in vivo and in vitro models often fail to capture human brain function. Innovative model systems—including digital reconstructions, embodied simulations, and new biological models—are needed.
Neuroscience
Clinical Trials are Inefficient, Slow and Scarce
Physiology and Medicine
Clinical trial designs are often inefficient, resulting in high costs, lengthy timelines, and suboptimal patient outcomes. Innovative trial designs and decision-support tools are required to streamline the clinical evaluation process and accelerate therapeutic development.
Physiology and Medicine
10
Our Immune System Can Uniquely Recognize Nearly Any Molecule but We Don’t Know the Recognition Code
Immunology
A better understanding of how the immune system interacts at the molecular level with threats and triggers is critical. This knowledge would enable the development of predictive tools and technologies to augment immune responses—improving interventions against infections, cancers, and autoimmune disorders.
Immunology
Cellular and Biomolecular States Are
Highly Multimodal and Complex
Cellular and Molecular Biology
Cellular state is a multifaceted and complex phenomenon, involving multiple overlapping omics layers that vary in time and space. Capturing and representing this multimodal complexity is essential for predictive modeling of cell behavior and for advancing our understanding of cellular function.
Cellular and Molecular Biology
Our Immune Memory Contains a Detailed History of Exposures but We Can’t Read It
Immunology
Immunological diseases often have nonobvious, complex etiologies and pathophysiologies that are difficult to identify.
Immunology
We Can’t Take High-Resolution Movies of or Intervene in Brain Computation at the Single Neuron Level
Neuroscience
Capturing the dynamics of large brain networks at single-neuron resolution in vivo is extremely challenging. Advanced imaging methods that record fast, high-resolution activity without destructive intervention are required to unravel the complex interplay of neuronal circuits in real time.
Neuroscience
Most of the Human Brain Remains Inaccessible
Neuroscience
Large portions of the living human brain are difficult to observe and modulate with current technologies. Safer, noninvasive, or minimally invasive methods are needed to capture real-time brain state information.

One funding program dedicated to making advancements in this space is that of ARIA (UK science R&D agency), which launched the Scalable Neural Interfaces opportunity space to support a new suite of tools to interface with the human brain at scale.
Neuroscience
Limited Ability to Image Molecules in Their Native Contexts
Cellular and Molecular Biology
We are currently limited in our ability to image molecules in their native contexts—for example, within live 3D tissues. Achieving scalable, high-resolution imaging of biomolecules in situ would de-risk many areas of biomedical science by enabling integrative, comprehensive molecular mapping within intact specimens.
Cellular and Molecular Biology
Fraud in the Scientific Literature
Metascience
Scientific literature is plagued by fraudulent publications, undermining trust and slowing progress.
Metascience
94
Modeling Mechanical Systems is Hard
Mechanical Engineering
The simulation and modeling of complex mechanical systems is challenging due to the intricate interplay of multiple physical phenomena. Improved computational models can enhance design and optimization.
Mechanical Engineering
45
Lack of Applied Synthetic Biology Platforms
Synthetic Biology
Applied synthetic biology is underutilized in applications such as building sustainable food systems and repairing the environmental damage caused by conventional agriculture and industry. Despite advances in tools and chassis engineering, there are few robust platforms that translate synthetic biology into scalable, field-ready solutions. This includes not only the production of low-impact proteins and agricultural inputs but also bioremediation technologies for legacy pollutants—such as pesticide-laden soils, heavy metals, and nutrient runoff—that degrade ecosystems and constrain land use. A new generation of synthetic biology platforms is needed to address both sides of the problem: replacing harmful production methods and cleaning up their long-term consequences.
Synthetic Biology
33
Frontier Telescopes Are Expensive and Take Decades to Build
Astrophysics
The current model for building space telescopes is cost-prohibitive and slow, often requiring decades of development. New approaches that exploit reduced launch costs and modular assembly are needed to accelerate telescope construction and reduce costs, and there needs to be the organizational structure and hunger to adopt such methods.
Astrophysics
62
AI Could Be Misused
Computation
The risk of AI being misused—whether through malicious intent or unintended consequences—necessitates robust safeguards and countermeasures.
Computation
52
Challenges in Tracking and Restoring Resilient Ecosystems
Ecology
Regenerating degraded environments and designing self-sustaining systems require a unified understanding of ecological dynamics. Our current models fall short in predicting complex interactions—such as feedback loops and stability thresholds—that determine ecosystem behavior.

To close this gap, we need better datasets and models of biodiversity and animal movements, as well as tools to predict and contain invasive species. We also need the ability to experiment with restoration strategies, and validate approaches ranging from rewilding to engineering de-extinction technologies.
Ecology
74
Uncertainty and Noise in the Science of Room-Temperature Superconductivity
Physics
There remains significant uncertainty over whether metallic hydrogen can exhibit room-temperature superconductivity at reasonable pressures, and measurements of other systems have been irreproducible and fragmented.
Physics
69
Underdevelopment of Modern Tools in the Social Sciences
Social Science
The social sciences need new tools to help researchers identify and prioritize important questions that will have an impact, and better infrastructure to collect qualitative data. Qualitative methods are powerful for understanding the how and why behind social outcomes, yet even the most comprehensive surveys don’t capture all the factors that contribute to social outcomes. AI-enabled qualitative methods could super-charge the social sciences, but there is much work to be done.

Similarly, many archaeological methods remain manual and lack the technological revolution seen in other fields, limiting discovery and analysis.
Social Science
89
Inability to Comprehend and Synthesize the Entire Scientific Literature at Scale
Metascience
The volume of scientific publications is overwhelming, making it difficult for humans to read, comprehend, and synthesize the entire body of literature. How can AI-generated knowledge become cumulative? What should a machine-human shared Wikipedia look like? We should collect and synthesize all the world’s knowledge, accelerate its development, and make it universally available in a compelling form.
Metascience
95
Proving Math Theorems is Challenging for Both Humans and AI
Computation
Both human mathematicians and current AI systems struggle with proving complex math theorems. Enhancing theorem proving through interactive and automated methods could push the boundaries of mathematical reasoning.
Computation
50
Policy Creation and Evaluation is Manual and Suffers from Low Efficiency and Accountability
Social Science
Policy development and evaluation processes today rely heavily on manual human review to ensure accountability. However, as AI systems increasingly support or automate these processes, this human-centered accountability becomes challenging. Human reviewers risk becoming a critical bottleneck, slowing policy implementation. New tools are needed to streamline policy creation and evaluation, and to ensure consistency and compliance before deployment.
Social Science
88
Many Methods Are Stuck in 20th Century Fabrication Paradigms
Mechanical Engineering
Modern manufacturing systems largely rely on paradigms developed in the last century where large machines produce components smaller than themselves. This approach is increasingly limited by scaling challenges and cost inefficiencies. To meet future demands, we need to reimagine manufacturing by developing universal robotic construction systems and low-capital, high-energy manufacturing solutions that leverage emerging technologies such as advanced robotics, precision machining, and renewable energy integration. These innovations could, for example, dramatically lower the cost of machining high-performance materials like titanium or enable widespread automation in sectors like desalination.
Mechanical Engineering
47
Incomplete Resolution of the Possibility of Low-Energy Nuclear Reactions
Physics
While low-energy nuclear reactions (LENRs) have received substantial attention and there is no good evidence they exist, there may still be other mechanisms or parameter combinations that are underexplored.
Physics
71
Our Platforms for Civic Engagement and Democratic Decision-Making Don’t Take Advantage of 21st Century Scalable Technology
Social Science
Our current systems for democratic participation are hindered by outdated platforms and tools that fail to scale with modern needs. Limited survey infrastructure, insecure voting methods, and under-informative deliberative tools restrict our capacity for informed, collective decision-making. By harnessing AI to facilitate clearer expression of public opinion and leveraging innovative technologies for secure, scalable engagement, we can transform civic participation into a more robust, effective, and inclusive process.
Social Science
87
Ephemeral Societal Data on Proprietary Platforms
Social Science
Much critical data is stored on proprietary platforms and is at risk of disappearing, hindering long-term research and reproducibility.
Social Science
93
When We Put a Molecule in the Human Body, We Can’t Predict What It Will Do
Physiology and Medicine
Drug development is often hampered by failures related to absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox). Improved predictive models for molecular interactions are essential for designing safer, more effective drugs, as well as evaluating the impact of environmental chemicals.

Additionally, there is a significant gap in our knowledge of what exactly is present in foods and how these components affect human biology. A comprehensive mapping of the “foodome” and studies on food component functionality are needed to advance nutrition science and personalized dietary interventions.
Physiology and Medicine
15
Limited ability to identify molecular structures through spectroscopy
Chemistry
Most molecular structure determination methods lose critical information, and solving the inverse problem remains challenging. This limits our ability to accurately reconstruct molecular structures from spectral data.
Chemistry
23
Manual and Laborious Nature of Chemical Synthesis
Chemistry
Chemical synthesis remains largely manual, limiting throughput and reproducibility. The field requires robust automation to accelerate discovery and production of new molecules.
Chemistry
29
Quantum Gravity is Experimentally Hard to Constrain
Physics
Quantum gravity remains elusive, with experimental constraints hindered by the need for extremely large-scale or prohibitively expensive experiments.
Physics
70
Microbes Quickly Out-Evolve Our Defenses
Biosecurity
Pathogenic microbes evolve quickly, and bad actors may exploit biotechnology for harmful purposes. Our current defenses struggle to keep pace with these evolving threats.
Biosecurity
80
Inadequate Blockers of Transmission
Biosecurity
Our ability to block the transmission of pathogens is limited. Without effective strategies, airborne and surface-based transmission continues to spread diseases. A meta roadmap is here.
Biosecurity
81
Difficulty Delivering Physical Probes for Imaging into Living Cells
Biophysics
Delivering physical probes for imaging into living cells is challenging due to barriers in cell membranes and potential perturbation of cellular function. New approaches are required to enable high-dimensional biosensing without invasive probes.
Biophysics
20
Inadequate Interventions for Greenhouse Gas Removal
Geophysics and Climate
We need more effective approaches to removing greenhouse gases from the atmosphere to mitigate climate impacts. However, challenges remain in harnessing natural carbon removal systems—due to difficulties in accurately measuring their environmental impact—and in reducing methane emissions from sources like the cow rumen. Innovative strategies, including modifying cow microbiomes and deploying scalable measurement and validation platforms, are essential to advance greenhouse gas removal efforts.

See also:  https://www.bezosearthfund.org/news-and-insights/bezos-earth-fund-releases-global-roadmap-to-scale-greenhouse-gas-removal-technologies and https://gaps.frontierclimate.com/
Geophysics and Climate
60
Bioengineering is Still Done Manually
Mechanical Engineering
Despite advances in automation, many bioengineering processes remain highly manual, limiting throughput and reproducibility in laboratory settings.
Mechanical Engineering
44
Particle Accelerators Are Large and Expensive
Physics
Traditional particle accelerators are enormous and costly, limiting experimental flexibility. Compact, benchtop accelerators could democratize high-energy physics and open new avenues in applications such as medical isotope production.
Physics
66
Protein Design Has Been Limited to Static, Bio-mimetic Structures
Synthetic Biology
Protein engineering has largely focused on designing static structures that closely mimic natural proteins. This narrow approach limits the creation of truly novel or highly functional enzymes.
Synthetic Biology
30
Higher-Resolution Views of the Universe Are Roadblocked by Formation Flying Technology
Astrophysics
Space telescopes offer vastly superior sensitivity to ground-based systems, but enhancing their resolution requires spacecraft with sub-micron precision.

Angular resolution of telescopes is limited by the size of the primary optic. Coherent aperture synthesis (interferometry) gets around this by coherently combining signal from separated telescopes where the resolution is proportional to the baseline separation. This has been very successful in the radio (see Event Horizon Telescope) but in the optical regime requires extremely difficult optomechanics and controls, and the sensitivity on the ground is inherently limited by the coherence time of the atmosphere.
Astrophysics
65
We Can’t Yet Replicate Animal Olfaction Synthetically as a Sensing and Classification Modality
Chemistry
We currently lack a comprehensive model explaining how biological systems decode and classify chemical signals through olfaction. Understanding this process is critical for applications ranging from flavor science to disease diagnostics to understanding and harnessing animal communication.
Chemistry
28
Light Scattering in Living Tissue Prevents Optical Access to Deeper Regions
Biophysics
Living tissue exhibits strong light scattering, which hampers deep-tissue imaging and limits resolution. Overcoming this barrier is critical for mapping neural activity and enabling noninvasive diagnostic imaging.
Biophysics
19
Much of the Biosphere Remains Uncharted and Vulnerable to Information Loss
Ecology
Much of Earth's biosphere—from the deep ocean to atmospheric bioaerosols—remains unexplored, with the microbial majority largely uncharted. Advancing new exploration technologies and systematically cataloging the Earth's microbiome could unlock discoveries of new life forms and biological insights that could impact health, climate, geoengineering, agriculture, and fundamental biology.
Ecology
75
Limited Diagnostic Tools Optimized for Low-Resource Settings
Global Health
Current diagnostic tests are costly or often offer only limited information, failing to reveal the cause of disease and delaying or preventing administration of available treatments. Moreover, early detection systems for emerging pathogens are fragmented, delaying critical public health interventions.
Global Health
100
Lack of Structure Prediction for Highly Dynamic Proteins
Biophysics
Current structure prediction tools like AlphaFold excel for stable proteins but struggle with highly dynamic proteins whose structures fluctuate continuously, leaving a gap in our understanding of intrinsically disordered proteins and protein allostery.
Biophysics
17
Inability to Anticipate or Prevent Ecosystem Tipping Points
Ecology
We lack the models and infrastructure to monitor and predict how ecosystems behave under stress or when they might collapse, as well as what metrics to use to determine that restoration is effective. We need to understand the underlying dynamics, feedback loops, and thresholds that lead to ecosystem degradation/ collapse, as well as to secure essential systems like pollination.
Ecology
73
Understanding Life as a Far-From-Equilibrium Physical Phenomenon
Biophysics
Our ability to analyze organisms holistically as systems which emerge from fundamental physics is limited by our lack of formal frameworks for distinguishing living and nonliving systems which are precise enough to be useful for practical scientific problems
Biophysics
22
Robot Hardware and Software is Still Clunky
Mechanical Engineering
Robots have the potential to revolutionize manufacturing, logistics, and many other industries—but only if they are both affordable and capable of high performance. Today’s robotic hardware is often prohibitively expensive and built using legacy designs that do not prioritize cost reduction, modularity, or scalability. Moreover, many robots struggle with dexterity and tactile sensing, and current design practices decouple hardware and software, preventing a co-evolution that could unlock new performance regimes. Overcoming these limitations requires a rethinking of both robot morphology and control, with an emphasis on integrated design, cost-effective production, and enhanced functionality.
Mechanical Engineering
46
Labor-Replacing AI Could Lead to Human Disempowerment
Social Science
As AI systems become the cornerstone of competitive advantage, they can inadvertently marginalize human roles and decision-making. The drive for efficiency and cost reduction may lead organizations to rely predominantly on AI, sidelining human judgment, creativity, and accountability. This dynamic risks creating environments where economic and social inequities widen, and the intrinsic value of human input is systematically undermined (see examples). The gradual disempowerment of individuals under such competitive pressures poses significant challenges for societal well-being and democratic governance.

See: https://gradual-disempowerment.ai/
Social Science
86
Synthetic Biology Platforms Are Over-Reliant on Evolved Cells That We Don’t Fully Understand or Control
Nanoscale Fabrication
We currently perform synthetic biology using naturally evolved (“kludgy”) cells rather than truly bottom-up engineered cells. This bottleneck limits our ability to design fully customizable biological systems.
Nanoscale Fabrication
35
Insufficient Monitoring and Modeling of Climate Processes and Control Paths
Geophysics and Climate
We have limited capacity to predict key disruptive events, such as solar flares that threaten power grids and communications, alongside an incomplete understanding of natural processes (atmospheric, ocean, etc.) that underpin climate models. We need better monitoring tools for characterizing phenomena that impact climate dynamics, such as aerosol-cloud interactions, and assessing potential interventions such as marine cloud brightening. These issues underscore the need for enhanced observational tools and more sophisticated models of climate processes.
Geophysics and Climate
57
Limited Microbial Hosts/Chassis Organisms
Synthetic Biology
Scientists are constrained to a small number of microbial hosts for bioproduction, limiting the diversity and efficiency of engineered biological systems. Expanding the repertoire of microbial hosts could unlock novel biochemical pathways, enabling the production of a wider array of biomolecules and improving the efficiency of biosynthetic processes. It is important to address any biosafety and biosecurity risks associated with developing such technologies.
Synthetic Biology
31
Doing and publishing research is expensive and subject to structural roadblocks
Metascience
Traditional structures dominate in how research is conducted and how its outputs are disseminated. Expensive publishing practices restrict and slow the spread of knowledge. We should replace outdated publishing practices and complement research practices with new approaches that leverage frugal innovation, community-led platforms, and open access. We imagine a future where scientific discovery is more inclusive and dynamic.
Metascience
96
Robust and Compact Plasma Confinement for Fusion is Still Not Solved
Physics
Stable plasma confinement is a major obstacle in achieving practical fusion energy. Advanced control systems and novel confinement techniques are needed.
Physics
68
We Don’t Have Easy Programmable Synthesis of Bio Polymers Other Than Nucleic Acids
Chemistry
While long-chain nucleic acid synthesis is advancing rapidly, the programmable synthesis of other polymers remains underdeveloped, limiting our capacity to design and produce diverse synthetic polymers.
Chemistry
27
Major Planetary Science and Astrobiology Missions Are Not Realized by Existing Government Space Agencies
Astrophysics
Some of the most important planetary science and astrobiology missions remain unrealized by traditional government agencies like NASA. Alternative, independent initiatives are needed to explore these high-priority scientific questions.
Astrophysics
63
AI is Still Narrow in its Reasoning and Planning
Computation
Current AI systems exhibit narrow reasoning and planning capabilities compared to human cognition. Broadening AI training methods to include holistic, brain-inspired architectures and cognitive frameworks can advance general intelligence (flagging that there is an AI safety risk here).
Computation
54
Inability to Program Complex Organisms and Developmental Pathways
Synthetic Biology
Current genetic tools primarily enable modification of simple organisms. Programming more complex organisms and orchestrating entire developmental pathways remains a major challenge.
Synthetic Biology
32
Risks of Malicious Bioengineering
Biosecurity
Advances in synthetic biology have unlocked unprecedented innovations, but also raise concerns about the potential for harmful bioengineering. Preventing misuse requires robust screening and control measures around DNA synthesis. Implementation must be coordinated and universal to effectively minimize the risk of malicious actors.
Biosecurity
83
Lack of a Dedicated Field for Planetary Terraforming
Space Engineering
There is currently no established field for systematically studying and applying planetary terraforming methods, leaving key challenges in transport, energy supply, and civil engineering largely unaddressed.
Space Engineering
78
We Can’t Safely and Controllably Deliver Complex Molecular Payloads to the Targets We Want in the Body
Physiology and Medicine
Current in-vivo delivery systems (viral vectors, nanoparticles, microchips) face challenges such as off-target accumulation and inefficiency, particularly in delivering therapies to the brain. Novel delivery approaches are needed to improve targeting and performance.
Physiology and Medicine
12
Under-Provisioning of Antibiotics, Vaccines and Other Interventions for Major Global Health Challenges
Global Health
Many of the world’s most deadly diseases—such as tuberculosis, Group A Streptococcus, hepatitis C, hepatitis B, and syphilis—lack effective vaccines or cures. Additionally, the pace of developing effective, low-cost, therapeutics for emerging pathogens in low resource settings is too slow to meet global health needs. Malnutrition exacerbates susceptibility to disease and impedes recovery; food security is important especially for early child development. Understanding the basic science of malnutrition during development is important for the development of more effective interventions.
Global Health
99
Live Cell Imaging at Deep Nanoscale Resolution is Destructive
Biophysics
Techniques that achieve deep nanoscale resolution in live cell imaging often destroy the sample, limiting the ability to conduct longitudinal studies on the same specimen.
Biophysics
21
Biological Life is Our Only Working Example of Complex Evolved Computation
Computation
Biological systems are the sole example we have of complex, evolved computation. Replicating this level of complexity in digital systems could unlock entirely new computational paradigms.
Computation
55
Education Modalities Suffer From Scaling Limitations
Social Science
Current education systems face structural inefficiencies such as excessive administrative workloads on educators, overcrowded classrooms, and inequitable resource distribution. Innovative technologies have the potential to significantly reduce these burdens by providing tools that assist teachers with scheduling, grading, and creating personalized, adaptive lesson plans. Digital platforms could dynamically tailor learning experiences to individual student progress, complementing classroom teaching. Additionally, technology-driven improvements in administrative efficiency could free valuable resources, enhancing educational equity and overall student experiences.

“US K-12 teachers are 30% more likely to face burnout than U.S. soldiers, whose lives are defined by relentless duty, perpetual war and low wages.” - Adrienne Williams

“Given recent improvements in the quality, affordability, and usability of technologies like AI, computer vision, and AR/VR, we can reimagine a more personali...
Social Science
90
Lack of Direct Measurement of Quantum Effects in Biological Systems
Biophysics
Despite theoretical predictions, quantum effects in biological systems remain largely unmeasured. Direct experimental evidence is needed to explore how quantum phenomena influence biomolecular interactions.
Biophysics
18
Current Chip Fabrication Methods are Extremely Expensive and Hard to Change
Nanoscale Fabrication
Modern chip fabs are enormous, multi-billion-dollar facilities with limited versatility in what they can produce. This bottleneck restricts the ability to create assemblies with diverse molecular components on a small scale.
Nanoscale Fabrication
37
Many Molecules Can’t Easily Be Crystallized
Materials Science
Crystallization is crucial for determining molecular structure, yet many molecules resist forming crystals. Improved computational models of crystal growth are needed to guide experimental efforts.
Materials Science
39
Designing Manufacturing Systems is Hard
Mechanical Engineering
Modern manufacturing system design remains complex, with traditional methods relying on outdated processes. AI-based design approaches have the potential to reimagine these systems without relying on the legacy of humanoid robots.
Mechanical Engineering
42
AI Could Go Rogue
Computation
The potential for AI systems to behave unpredictably or dangerously (“go rogue”) is a critical concern. Ensuring safe and controllable AI architectures is essential for reliable operation.

See also:
• https://www.lesswrong.com/posts/fAW6RXLKTLHC3WXkS/shallow-review-of-technical-ai-safety-2024
• https://deepmind.google/discover/blog/taking-a-responsible-path-to-agi/
Computation
51
Our Measurements and Tests Aren’t Revealing What Is Actually Causing Many Diseases
Physiology and Medicine
Our understanding of human physiology and disease remains incomplete. In the last century, we have developed cures for many diseases with well-defined root causes (polio, smallbox, cholera, SMA, cervical cancer, etc.). However, a wide array of conditions still eludes cures and treatments. We have yet to fully decipher the dynamic interplay between brain and peripheral systems, the bioenergetic processes underlying chronic conditions, and the multifactorial pathways that drive aging. The biological mechanisms driving complex diseases and the aging process are multifactorial, involving multiple interacting pathways.

Although we understand some individual aging mechanisms, we do not yet have line of sight to comprehensively rejuvenating mammals or extending lifespan. To overcome these challenges, we need combinatorial approaches that can modulate multiple mechanisms simultaneously, allowing us to measure multi-system impacts and develop effective interventions.
Physiology and Medicine
14
Inadequate Imaging of Material Structures
Physics
Many materials’ internal structures are difficult to image with current technologies, limiting our understanding of their properties at the nanoscale.
Physics
67
Our Compute Stack is Insecure but Fundamentally Doesn’t Have To Be
Computation
Insecure software can lead to vulnerabilities that undermine the reliability and safety of computational systems. Formal methods and rigorous verification are needed to synthesize secure software.
Computation
53
We Have a Limited Ability to Acquire, Concentrate and Substitute Chemical Elements in Processes
Materials Science
The cost of materials is often dominated by the cost to obtain their constituent elements. What presents commercially as the “critical minerals problem” masks a larger scientific bottleneck on how we acquire, concentrate, and substitute chemical elements.
Materials Science
41
Fragile Supply Chains and Lack of Backup for Critical Infrastructure
Biosecurity
Many critical supply chains and infrastructure systems are fragile and lack robust backup mechanisms, leaving society vulnerable.
Biosecurity
84
A Limited Set of Rigid Organizational Structures for Organizing and Funding Research Constrains the Forms of R&D That Get Done
Metascience
This is more of a meta-bottleneck. But scientists are spending a lot of time not doing science, and the institutional structures in which they work are often set up with incentive structures that hinder certain kinds of outcomes, like more coordinated research.
Metascience
98
Insufficient Surveillance of Bio-Threats
Biosecurity
Rapid detection of emerging bio-threats is critical for effective intervention and containment. However, many pathogens are detected only after widespread transmission has occurred. In addition, attributing the source of these threats remains challenging.
Biosecurity
82
Inability to Model Turbulence
Physics
Modeling turbulence remains one of the most challenging problems in physics due to its nonlinear and chaotic nature.
Physics
72
Lack of Infrastructure Technologies and Strategies Optimized for Low-Resource Settings
Global Health
Global health outcomes are compromised by insufficient health systems and infrastructure that limit our ability to prevent and control infectious diseases. Key deficiencies include the lack of cost-effective antimicrobial materials to block pathogen transmission, underdeveloped intervention models for effective public health strategies, and outdated sanitation solutions that fail to meet the needs of vulnerable populations.
Global Health
101
Underdevelopment of Deep Tooling for Economic Modeling and Future Forecasting
Social Science
Current economic models are often too simplistic to capture the intricate dynamics of our global economy, limiting effective policy-making and forecasting. Experimentation with innovative economic models—such as those incorporating universal basic income or alternative market systems—is rare, leaving us unprepared for emerging trends. The inherent complexity of global systems further complicates accurate forecasting, underscoring the urgent need for more sophisticated, adaptive tools that can better predict and navigate the economic landscape of tomorrow.
Social Science
91
Designing Buildings is Hard
Mechanical Engineering
Architectural design and construction planning are complex and labor-intensive. Advanced computational design and AI-driven optimization have the potential to revolutionize how buildings and construction plans are generated.
Mechanical Engineering
43
Sim-to-Real Transfer for Robots is Hard
Mechanical Engineering
Bridging the gap between simulated robot behavior and real-world performance remains a significant challenge, particularly for tactile interactions and complex environments.
Mechanical Engineering
48
Outdated Space Station Construction
Space Engineering
Only one new space station (天宫) has been launched this century, due to high costs and reliance on traditional, government-led megaprojects.
Space Engineering
77
Searching Through the Vast, Underexplored Space of Materials is Slow and Expensive
Materials Science
“New materials create fundamentally new human capabilities. And yet…new materials-enabled human capabilities have been rare in the past 50 years.” The core challenge lies in our inability to reliably design and manufacture materials that meet specific engineering requirements–and to do so at an industrial scale and reasonable cost.

Identifying promising new materials is hampered by the slow pace of exploration. The integration of machine learning, physics-based property prediction, and self-driving laboratories could dramatically accelerate this process. A significant opportunity lies in modeling the vast, unexplored space of potential materials in silico.
Materials Science
38
Poor Scalability of Bioreactors Limits Biomanufacturing
Synthetic Biology
Current bioreactor designs are inefficient when scaling up production processes, limiting the ability to produce bioproducts at industrial scales.
Synthetic Biology
34
Some Proteins Are Still Recalcitrant to Experimental Structure Analysis
Biophysics
Membrane proteins are notoriously difficult to analyze experimentally and to incorporate into technological applications due to their inherent insolubility in aqueous environments. Their recalcitrance limits our capacity to study their structure and function in detail. Other challenges include the difficulty of studying small proteins with cryo-EM.
Biophysics
16
Intervening in Earth Systems at Scale is Largely Untested
Geophysics and Climate
There are currently no direct interventions to address climate tipping points such as glacier melt, leaving some critical processes unmitigated. The fundamental science and engineering principles behind emergency climate interventions remain largely untested at relevant scales, limiting our preparedness for rapid climate change.

See: https://www.outlierprojects.org/
Geophysics and Climate
59
Inability to Perform Chemistry with Direct Positional Control
Nanoscale Fabrication
Our current methods do not allow precise control over the positional placement of atoms or groups during chemical synthesis, limiting our ability to build molecules with atomic precision. A general-purpose approach to atomically precise fabrication was envisioned by Drexler in the 1980s and Feynman in the late 1950s. DNA origami made a leap in 2006, but DNA is in some key ways a much less precise and versatile nanoscale building material than proteins/peptides. A promising path would extend “DNA origami” to “protein carpentry” by adapting Beta Solenoid proteins, or other modular protein components with programmable binding properties, as lego-like building blocks and then using the latter to construct massively parallel protein-based 3D printers for lego-like covalent assembly of a restricted set of chemical building blocks. This one is riskier: how programmably can we really control protein assembly, and could we bootstrap from initial crappy prototype protein-carpentry-and-or-DNA-ori...
Nanoscale Fabrication
36
Clinical Trials Are Poorly Optimized for Evidence Gathering
Metascience
Current clinical trial designs are not sufficiently optimized for gathering robust evidence, leading to inefficiencies and suboptimal outcomes.
Metascience
97
Limited Tools for Improving Individual, Social and Societal Epistemics in the Face of Misinformation
Social Science
In an era of relentless information overload and pervasive misinformation—fueled by algorithms that prioritize fleeting engagement over meaningful value—we have the opportunity to reshape our digital spaces. By leveraging AI and more intentional design of social media spaces for epistemic improvement, we can empower users to curate, evaluate, and contextualize content more effectively to create a healthier digital world.
Social Science
85
Translational Gaps in Development Economics
Social Science
There exists a disconnect between academic research and the practical implementation of development economics, hampering the conversion of theoretical insights into effective real-world interventions. Current mechanisms for delivering public goods and fostering collective cooperation are inefficient, limiting our capacity to coordinate resources and drive meaningful change. Innovative approaches are needed to bridge this gap, ensuring that cutting-edge economic theories can be transformed into actionable policies and scalable interventions that truly improve development outcomes.
Social Science
92
We Can Learn More from Nature’s Biological Designs
Ecology
Nature’s blueprints span from the unseen nanoworld to the enigmatic origins of life. Despite the incredible diversity of nanostructures, many remain hidden due to current imaging limitations. Likewise, the mysteries of animal communication—crucial for decoding behavioral cues and social structures—await breakthrough insights. Moreover, the primordial conditions of our planet, essential for understanding life’s genesis, are obscured by the absence of rocks from before 4.1 Ga and fossils before 3.5 Ga (although life almost certainly established itself on our planet before that). Addressing these challenges can unlock new understandings in biology, ecology, and more.
Ecology
76
Silicon Compute is Massively Energy Intensive Compared to Biological Brains
Computation
Modern deep learning and general computation demand enormous energy, limiting scalability and sustainability. Addressing energy efficiency is critical for the next generation of computing platforms, though it also supports potential proliferation of advanced AI and should be advanced alongside AI safety and governance considerations.
Computation
49
Limited Detection of Gravitational Waves Across the Frequency Spectrum
Astrophysics
Detecting gravitational waves allows us to observe cosmic events like black hole mergers and neutron star collisions that are invisible through traditional telescopes. Current gravitational wave detectors are primarily sensitive to audio-band signals. Some phenomena, including speculative ones such as high-frequency emissions from advanced propulsion systems, might only be detectable with novel approaches.
Astrophysics
64
We Lack Basic Capabilities that Are Necessary for Travel Far Beyond Earth
Space Engineering
We lack the many technologies to support exploration and survival off earth. Our exploration efforts remain confined to our solar system, limiting our potential to explore beyond and understand the broader cosmos.
Space Engineering
79
Limited Ability to Design and Scalably Synthesize Macroscale Materials
Materials Science
While many promising materials have been discovered in the lab, current synthesis methods are often too expensive to produce these materials in sufficient quantities. Some examples of novel materials that would be highly enabling include:

• Low activation, thermally conductive materials that are resistant to radiation damage are needed to enable fusion reactors (the first wall material is currently a limitation), spacecraft, etc.
• Materials that emit at the transparency window of the atmosphere (that were easy to apply like paint) to drastically diminish solar earth heating (example)
• Hyper-efficient thermoelectrics that could directly turn heat into electricity.
• Materials that autonomously heal to improve our infrastructure and prevent system failures due to material defects.
• Materials that have the insulating properties and high melting points of ceramics but the formability and ductility of metals for jet engines and atmospheric reentry vehicles.
Materials Science
40
Limited Understanding of the Chemical Reaction Space
Chemistry
Our overall knowledge of the chemical reaction space, including the catalysts that drive these reactions, is still rudimentary. We also lack detailed the large materials synthesis and processing datasets needed to enable highly predictive models.
Chemistry
26
Inadequate Emergency Climate Interventions and Response
Geophysics and Climate
There is a critical need for more precise, rapid, and localized climate intervention strategies. Current approaches lack the fine-grained models and rapid response mechanisms required to adapt to diverse climate impacts, such as heatwaves, which demand swift and effective action. The ability to control local weather phenomena—including cloud formation and hurricanes—could help mitigate climate risks.
Geophysics and Climate
58
Inability to Image Materials Atom by Atom
Chemistry
Many current imaging techniques lack the resolution to image materials on an atomic scale, limiting our understanding of material properties at the most fundamental level.
Chemistry
25
In-Silico Molecular Simulation Is Slow and Kludgy
Chemistry
In-silico molecular simulation has not received the necessary push, despite the promise of machine learning-based surrogate models. Moreover, advancements in quantum chemistry—both AI accelerated and quantum/ASIC-enabled—remain underexploited.
Chemistry
24
Limited Longitudinal Data in Humans
Physiology and Medicine
A comprehensive understanding of human health over time is hindered by the lack of longitudinal data from cohorts that are diverse and globally representative. Such datasets are essential to track developmental, nutritional, and environmental influences on long-term health outcomes.
Physiology and Medicine
13
Inadequate Models of Human Physiology
Physiology and Medicine
Current preclinical models of human physiology, including animals and organoids, do not fully capture the complexity of human physiology, limiting the predicting power of preclinical experiments and explaining, in part, the costly failures of drug development in clinical trials. This is especially true for complex disorders including those of aging, neurological disorders, and female reproductive biology. More systematic and representative models—including ex vivo human organ systems or even whole bodies and novel animal species—are needed to improve the predictive power of biomedical research. These technologies also have applications in addressing organ shortages, improving neonatal care, and other unmet medical needs.
Physiology and Medicine
11
Outdated and Fragmented Recycling, Cleanup and Bioremediation Systems
Geophysics and Climate
We need to improve our management of natural systems. The world's oceans suffer from extensive pollution, undermining marine ecosystems and disrupting global climate processes. Inefficient wildfire management is a prime example of problematic management of natural fire cycles.
Geophysics and Climate
61
Insufficient Integrated Earth Climate Models
Geophysics and Climate
Current models struggle to accurately predict climate tipping points due to the intricate interplay of diverse climatic factors, hindering proactive intervention efforts. Additionally, designing optimal climate control strategies is challenging because of the nonlinear and multifaceted interactions among economic, technological, and social factors.
Geophysics and Climate
56
Artisanal Nature of Experimental Physics Platforms
Physics
There is a lack of open and repeatable tooling to spread experimental physics into new areas, e.g., can ultracold atoms be more readily leveraged by people outside a small set of quantum physics labs to pave the way for more applied uses?
Physics
102
Silicon-Based Electronics Face Fundamental Limits in Dimensional Scaling
Computation
For over five decades, silicon-based CMOS technology has driven unprecedented progress in computing and information technology through dimensional scaling following Moore's Law. This miniaturization has led to exponential increases in transistor density, performance, and energy efficiency. However, as transistor channel dimensions shrink below a few nanometers, silicon and conventional bulk semiconductors (e.g., SiGe, III-V materials) are encountering insurmountable fundamental physical and material limits (heat dissipation, short-channel effects, etc.).
Security Risk
Safety Risk
Computation
104