The four-axis ranking
We rank humanity’s most important problems on four quantifiable dimensions — quantity of humans affected, severity per capita, current solution quality, and addressable market size — and package each as a proposal in the spirit of Musk’s Hyperloop Alpha. This document is the proposal for biosecurity & pandemic preparedness. Every number below is sourced and tagged with confidence. Every ranking is a conjecture, open to refutation.
Quantity · humans affected
8.1B
highSeverity · WTP / wealth
85%
lowCurrent solutions
3.0 / 10
medMarket size · TAM
$100.0B
lowWhat we are trying to solve
COVID-19 demonstrated the tail risk from a single pathogen. Dual-use gene synthesis, lab leaks, and deliberate misuse mean that worst-case pandemics could be civilization-ending. Tractable: far-UVC sterilization, early-warning surveillance, broad-spectrum countermeasures, pathogen-agnostic detection.
The gap between the world and the world that is physically possible
Today: World detects novel pathogens months after they spread; vaccines take 12+ months to develop and longer to globally distribute.
Current solution quality is rated 3.0 / 10 (med confidence) — meaning there is substantial unclaimed ground between what exists and what is possible. estimated — decent reactive vaccines but pathogen-agnostic detection + rapid global distribution still weak.
Who is already working on this
4 entities are currently working on this problem across public markets, private companies, and research orgs. Each is evidence the market is real; none has obviously solved it.
Moderna
public · USAmRNA platform company. Pandemic preparedness via rapid vaccine development, plus pipeline in malaria, HIV, and rare disease.
$10.5B
Ginkgo Bioworks
public · USACell programming platform. Biosecurity Division runs metagenomic surveillance and pathogen detection at scale.
$350M
Colossal Biosciences
private · USADe-extinction and genetic engineering. Biosecurity adjacency via rapid genome editing and cold-chain logistics.
$10.2B
If we solve this, here is the world we get
After · 10 years
Pathogens detected within days via genomic surveillance; vaccines designed and manufactured in weeks; equitable global distribution. No mass-casualty pandemic events possible.
Requests for startups · 3 concrete companies to build
Pathogen-agnostic early warning
We detect outbreaks by waiting for humans to get sick and show up at hospitals — weeks late, by design. Build the metagenomic sampling network that flags any novel replicating pathogen in days.
- why now
- Sequencing cost fell below the threshold where continuous environmental metagenomics is economically routine.
- shape
- A network of wastewater, airport, and air-handler samplers feeding a continuous metagenomic pipeline that alarms on any novel exponentially-growing genome — known or unknown.
- success
- Time-to-detection for a novel pathogen drops from weeks to days, globally, before the first hospital wave.
Days-not-months vaccine manufacturing
mRNA proved the design step can take hours. Manufacturing, fill-finish, and distribution still take a year. Build the distributed, rapidly-reconfigurable biomanufacturing stack that closes the gap.
- why now
- Cell-free and benchtop synthesis matured; the constraint is now industrialization, not science.
- shape
- Containerized, standardized micro-factories + a regulatory playbook that lets a validated process move from sequence to vialed doses in days, near the point of need.
- success
- A new vaccine reaches a billion arms within weeks of pathogen identification, not within years.
Far-UVC as building infrastructure
We treat indoor airborne transmission as a fact of life. It is not — it is an untreated utility. Build the far-UVC + ventilation retrofit company that makes indoor air as safe as treated water.
- why now
- Far-UVC safety data matured and 222nm excimer cost is on a manufacturing learning curve.
- shape
- A retrofit + new-build company that designs, installs, and certifies far-UVC + ventilation for schools, transit, and offices, sold on insurance and absenteeism economics.
- success
- Airborne transmission indoors becomes as rare as cholera from tap water in developed economies.
full rubric + framing on the Requests for Startups page.
What the market can pay
The world is already paying $100.0B per year against this problem (projected global biosecurity + pandemic-prep market (vaccines, surveillance, broad-spectrum countermeasures, PPE) at full deployment; low confidence).
A successful solution does not need to capture more — it needs to redirect a meaningful slice of existing spend, plus the latent willingness-to-pay implied by the severity score above. The cost ceiling for a real solution is bounded by this number; everything cheaper is dominated, everything more expensive is a non-starter.
What could go wrong, and how we know we are not wrong
Section in progress
Failure modes, ethical considerations, and the conditions under which this whitepaper would be falsified are being authored as the weekly cadence ships. The Deutschian commitment: every claim above is a conjecture; we publish the conditions under which we would update. New whitepaper sections ship with each Monday newsletter drop. Subscribe to get the upgrade, or contribute on GitHub.
Who would back this
Capital allocators with a stated thesis or deployed portfolio in this domain. This is a starting list — Exa Websets enrichment will expand it to direct check-writers per company.
Founders Fund
Contrarian hard tech that rebuilds the industrial base.
a16z American Dynamism
National-interest technology, aerospace, defense, manufacturing, public safety.
Lux Capital
Counter-conventional science at the edges of physics and biology.
What the thinkers say
“Funded Fast Grants during COVID to demonstrate that biomedical research can move at wartime speed when the structure allows it.”
“Bio-manufacturing and biosecurity are named hard-quest categories in the Founders Fund thesis and deserve high-agency builders.”
Where this is wrong, tell us
Every number on this page carries a source and a confidence tag. Every section open to refutation. If a citation is wrong, a number is stale, or a conjecture is unfounded — file a correction.
corrections → use the feedback widget in the nav · open issue at github.com/adamtpang/optimism.fun