166 billion potential treatments remain untested > “Sixteen years on, he has amassed the largest database of small molecules in the world, a gigantic virtual collection of 166 billion compounds.” > — Nature, 2017, How my race to find a drug for my daughter is helping others
3.5% participation tipping point > “The research found that nonviolent campaigns were twice as likely to succeed as violent ones, and once 3.5% of the population were involved, they were always successful.” > Alternative title: 3.5% rule academic source > “Chenoweth and Maria Stephan studied the success rates of civil resistance efforts from 1900 to 2006, finding that nonviolent movements attracted, on average, four times as many participants as violent movements and were more likely to succeed.” > — BBC Future, 2019, ‘The 3.5% rule’ | Wikipedia, 3.5% rule
Annual child deaths statistic > 15,000 are children (based on 5 million annual child deaths) > — UNICEF, 2024, Levels and trends in child mortality 2024 | Note: 4.8 million children under 5 died in 2023
Percentage of preventable deaths > 80,000 were preventable (53% of deaths are preventable) > — CDC, 2024, Preventable Premature Deaths from the Five Leading Causes of Death | Note: 53.8% figure is for unintentional injury deaths; overall 20-40% of deaths from leading causes are preventable
Active combat deaths annually > 2024: 233,597 deaths (30% increase from 179,099 in 2023) > Deadliest conflicts: Ukraine (67,000), Palestine (35,000) > Nearly 200,000 acts of violence (25% higher than 2023, double from 5 years ago) > One in six people globally live in conflict-affected areas > — ACLED: Global Conflict Surged 2024 | Washington Post via ACLED | ACLED Conflict Index
Annual cost of Afghanistan War: $300 billion > Single Year of Afghanistan War: $300 billion > — Brown University Costs of War Project, 2021, Costs of the 20-year war on terror | Note: $300 million per day × 365 days ≈ $109.5 billion/year; total war cost was $2.3 trillion over 20 years
Alphabet R&D spending: $40 billion > Alphabet/Google R&D spending: $49.3 billion (2024), $45.4 billion (2023) > 8.58% increase from 2023 to 2024 > — Statista: Alphabet R&D Costs | MacroTrends: Alphabet R&D > Note: Growth driven by personnel costs (thousands of new engineers) and AI investments
Annual deaths from Alzheimer’s and other dementias > Alzheimer’s | 2.6M deaths/year > — Alzheimer’s Association, 2024, Alzheimer’s Facts and Figures Report | CDC, 2021, FastStats - Alzheimers Disease | Note: 119,399 deaths in US in 2021; global dementia deaths estimated at 2.6M annually
Amazon R&D spending: $85 billion > Amazon “Technology and Infrastructure” spending: $88.5 billion (2024), $85.6 billion (2023) > Note: ~$21.5B (2024) is content production for Prime Video; true R&D is lower > Majority of 2024 capex ($75B) going to AWS and AI infrastructure > — RD World: Amazon R&D Spending | MacroTrends: Amazon R&D > Note: Amazon’s R&D spending exceeds that of entire country of France
Antimicrobial resistance deaths projection > “By 2050, 10 million lives a year and a cumulative $100 trillion of economic output are at risk due to the rise of drug-resistant infections if we do not find proactive solutions now to slow down the rise of drug resistance.” > — Review on Antimicrobial Resistance, 2016, Final Report
Animal diseases eradicated by veterinary science > Rinderpest eradicated in 2011 - only second disease ever eradicated after smallpox > Declared globally eradicated by UN FAO and World Organisation for Animal Health > “Greatest veterinary achievement of our time” - devastating livestock disease for centuries > — Our World in Data: Rinderpest Eradication | WOAH: Rinderpest > Note: Caused up to 90% mortality in affected herds. Eradication achieved through coordinated international vaccination campaign launched in 1994
Number of potential drug combinations tested annually > NCI ALMANAC evaluated 5,232 drug-drug pairs across 60 cancer cell lines (304,549 experiments) > DrugCombDB includes 448,555 drug combinations from high-throughput screening (2,887 unique drugs) > Theoretical scope: ~845,000 possible pairings from approved and developmental anticancer drugs > — PMC: DrugCombDB | PubMed: Drug Combination Prediction > Note: While hundreds of thousands of combinations have been tested in research, systematic clinical testing is far more limited
Annual pet food sales: $150 billion > Global pet food market: $151 billion (2024), up $20B from previous year > Market estimates vary by source: $130.8B - $151B depending on methodology > Expected to grow to $192.8B by 2033 (CAGR 4.4%) > — Statista: Pet Food Market | IMARC: Pet Food Market Report > Note: Strong growth driven by premiumization, humanization of pets, and increasing pet ownership globally
Annual R&D savings potential of $50 billion > Pharma R&D spending: $200B+ annually (2020s), up from $30B in 1990s > Development cost estimates: $81.4B/year (2018-2022) for first-in-class/advance-in-class drugs > Efficiency opportunities: Transformation could reduce costs “from billions to millions” per drug > Specific “$50B savings” figure not verified but significant efficiency potential documented > — CBO: Pharma R&D | Accenture: Transforming Pharma R&D | Clarivate: Pharma R&D Efficiency
Global anti-aging cream market: $50 billion > Global anti-aging products market: $50.92 billion (2024) > Market estimates range $48B - $76B depending on category definitions > Expected to reach $80.55B by 2032 (CAGR 5.9%) > — Data Bridge Market Research | Grand View Research > Note: Growth driven by aging populations, increased disposable income, and social media beauty standards
Antidepressant failure rates: Two-thirds fail to achieve remission > STAR*D trial: Only 28-33% achieved remission with first antidepressant treatment > About two-thirds of patients did not achieve remission with initial treatment > Cumulative remission after up to 4 trials: 35-67% (disputed) > Treatment-resistant depression defined as failure of two antidepressant trials > — Psychiatric Services: STAR*D Results | PMC: STAR*D Reexamination | Wikipedia: STAR*D
Market capitalization of Apple Inc. > Apple market cap: $3.92 trillion (Dec 2024), approaching $4 trillion milestone > Grew by $921 billion (+39%) in 2024 alone > World’s most valuable company, representing >3% of global stock market > — Companies Market Cap: Apple | Yahoo Finance: Apple $4T Milestone > Note: First company ever to reach $4T valuation. Growth driven by AI improvements to iPhone and other devices
Apple R&D spending: $32 billion > Apple R&D spending: $31.4 billion (2024), $29.9 billion (2023) > R&D intensity reached levels last seen before iPhone launch (early 2000s) > Increased $10B+ since 2020, driven by Vision Pro, Apple silicon, AI/ML investments > — Statista: Apple R&D Expenditure | MacroTrends: Apple R&D > Note: Apple has spent $183 billion on R&D in less than 12 years
U.S. Constitution Appointments Clause > Article II, Section 2, Clause 2: President nominates/appoints officers with Senate confirmation (principal officers) or Congress may vest appointment in President alone, courts, or department heads (inferior officers) > Major violations: Buckley v. Valeo (1976) - FEC composition; Lucia v. SEC (2018) - ALJs are officers; United States v. Arthrex (2021) - patent judges; Jack Smith special counsel case (2024) > Remedies: New hearing before properly appointed official; Congressional/executive correction > — Constitution Annotated: Appointments Clause | Justia: Appointments Clause | SCOTUSblog: Arthrex Remedy
ARPA‑H official site > “ARPA‑H funds high‑impact research to drive biomedical breakthroughs.” > — ARPA‑H, About
Poll on belief in astrology in the U.S. > 27% of U.S. adults believe in astrology (Pew Research 2024) > Belief higher among younger adults (37% under 30) and women (43% women 18-49 vs 16% men 50+) > Consistent range of 23-30% belief across multiple polls since 1990 > — Pew Research: Astrology Survey | YouGov: Astrology Belief > Note: About half (51%) don’t believe, 22% unsure. Belief not strongly correlated with religious affiliation
Australia medical research spending: $900 million > NHMRC Medical Research Endowment Account: $940 million (2024-25) > Medical Research Future Fund (MRFF): $24.5 billion long-term investment, $650M/year for new projects > Combined NHMRC + MRFF: ~$1.5 billion in research grants annually > — NHMRC Budget 2024-25 | MRFF Overview > Note: Total NHMRC funding exceeds $3.8B over budget and forward estimates to 2027-28
Average cost of a competitive U.S. Senate campaign > Median Senate reelection campaign (2024): $11.1 million > Highly competitive races: $90-97 million (e.g., Brown-OH, Tester-MT) > Average Senate candidate (2020): $27.2 million > — Issue One: 118th Congress Fundraising | OpenSecrets: Most Expensive Races > Note: Truly competitive battleground races cost ~10x the median. Senators in tight contests raised over $123K/day
Estimated deaths due to FDA delay in approving beta blockers > Beta blockers approved in Europe mid-1970s, FDA didn’t approve until 1981 > FDA estimated the drug could save 17,000 lives/year after approval > Estimated 100,000 deaths from secondary heart attacks during 6-7 year delay > — FDAReview.org: FDA Harm | Orange County Register: Death by FDA Delay > Note: FDA imposed moratorium due to possible animal carcinogenicity despite human clinical evidence from 1974
Examples of Biological Immortality and Extreme Longevity in Nature > Hydra: Biologically immortal - no mortality increase over 4-year study, kept alive 12+ years > Planarian worms: Somatically immortal with limitless telomere regeneration, clonal lines >15 years > Axolotls: Regrow limbs, brain parts, heart tissue through remarkable regeneration > Naked mole rats: Live 37+ years (10x similar rodents), cancer-proof, no age-related mortality increase > Bowhead whales: Live 200+ years, unique DNA repair mutations, extra cancer-suppression genes > — Wikipedia: Biological Immortality | PMC: Molecular Signatures of Longevity > Note: These animals demonstrate enhanced DNA repair, abundant stem cells, telomerase activity, and cancer resistance
Boeing Defense annual revenue > Boeing Defense, Space & Security: $24.93 billion (2023), ~$22-23B estimated (2024) > Q4 2024: $5.4 billion (20% decline from previous year) > — Statista: Boeing Defense Revenue | Boeing Q4 2024 Results > Note: Revenue decline in 2024 reflects broader challenges in Boeing’s defense operations
Bradley-Terry and PageRank Models for Ranking > Bradley-Terry: Probability model for pairwise comparisons (1952, earlier by Zermelo 1920s); maximum likelihood estimation > PageRank: Ranks nodes by importance in network via stationary distribution of Markov chain > Connection: Under quasi-symmetry, Bradley-Terry scores are equivalent to scaled PageRank; ML estimates can be approximated from limiting distribution > Applications: Sports rankings, journal citations, AI model rankings, consumer choice, search engines > — arXiv: PageRank and Bradley-Terry Model | Wikipedia: Bradley-Terry | ScienceDirect: Improving PageRank with Sports Results
Brazil medical research spending: $600 million > Major agencies: CNPq (federal), FAPESP (São Paulo - 1% of state tax revenue), CAPES > National “knowledge budget” declined from R$25.3B (2019) to R$17.1B (2022) > FAPESP is one of best-funded state research agencies in Brazil > — PMC: Brazil Biomedical Research Funding | DWIH: Brazil Research Funding > Note: Significant budget constraints in recent years; public entities remain main funding source
Brian Armstrong’s investments in health tech > ResearchHub (2020): Scientific research platform, raised $5M Series A (2023), uses crypto to incentivize research > NewLimit (2022): Longevity/aging company using epigenetic reprogramming, raised $130M > Funding CRISPR baby tech: First major commercial investment in gene-editing human embryos > — MIT Tech Review: Armstrong CRISPR Investment | Yahoo Finance: ResearchHub Funding > Note: Coinbase CEO using crypto wealth to fund radical health/longevity ventures. Co-founder Blake Byers advocates significant GDP spending on “immortality” research
BrightID social identity verification network > Privacy-first decentralized social identity network for proving unique personhood > Sybil-resistant through social graph analysis using modified SybilRank algorithm (GroupSybilRank) > Users build connections (“know well”, “just met”, “suspicious”) - matching responses verify authenticity > No personally identifying information recorded; pseudonymous across platforms > — BrightID | Frontiers: Sybil-Resistance in Proof of Personhood > Note: Compatible with 18 apps including Gitcoin, clr.fund, Snapshot. Early stage with challenges in decentralization and scalability
California direct democracy and ballot proposition overload > 2024: 7 measures pulled before election after back-room negotiations (16 since 2014) > System designed to curb special interests has instead empowered them > “Victory is on the side of the biggest purse” (1923 legislative committee) > Influx of special interest propositions makes ballots longer, more confusing, less accessible > — Carnegie Endowment: California Direct Democracy | Davis Political Review: Hijacking the Ballot > Note: Progressive Era reform meant to curb special interests has had unintended opposite effect
Canada Bill C-76 foreign influence restrictions > Elections Modernization Act (Bill C-76), royal assent December 13, 2018 > Foreign entities prohibited from spending ANY money to influence federal elections > Third parties banned from using foreign funds for partisan activities/advertising > Previously: foreign entities could spend up to $500; Now: $0 > Platforms/broadcasters prohibited from knowingly selling ads to foreign entities for electoral influence > — Elections Modernization Act (Wikipedia) | Canada: Combatting Foreign Interference | McCarthy: Canada’s Election Laws Changing
Canadian election expenditure reporting threshold over $500 > Third parties must register if spending >$500 on partisan activities/advertising in pre-election/election periods > Financial returns must report contributions >$200 including contributor identity > Donations >$200 must include name and address in political financing returns > Real-time disclosure exists at Ontario provincial level; federal uses scheduled reporting > — Elections Canada: Expense Limits | Elections Canada: Political Financing
Canada medical research spending: $1.5 billion > CIHR (Canadian Institutes of Health Research): $1.34 billion in grants/awards (2024-25) > Total parliamentary authorities: $1.43 billion (2024-25) > Budget 2024 adds $540.3M over 5 years, ramping to $229.2M/year by 2028-29 > — CIHR: Budget 2024 | CIHR Grants Expenditures > Note: CIHR invests 95% of funding directly in health research, only 5% on operating costs
Annual deaths from cancer (10 million) > Cancer deaths: 10.4 million globally in 2023 (9.7 million in 2022) > 18.5 million new cancer cases in 2023 > 65.8% of deaths occur in low- to upper-middle-income countries > — The Lancet: Global Cancer Deaths 2023 | WHO/IARC, 2024, Global cancer burden growing > Note: Cancer is the second leading cause of death globally after cardiovascular diseases. Projected to reach 18.6 million deaths by 2050 (74.5% increase)
California Consumer Privacy Act (CCPA) and California Privacy Rights Act (CPRA) > CCPA effective January 1, 2020; CPRA (Prop 24) approved November 2020, effective January 1, 2023 > Consumer rights: Know/access personal data; Delete data; Opt-out of sale/sharing; Non-discrimination; Correct inaccurate data (CPRA); Limit sensitive data use (CPRA) > Enforcement: California Privacy Protection Agency (CPRA created); Previously CA Attorney General > Penalties: Up to $7,500 per intentional violation; $2,500 per unintentional violation > — CA Attorney General: CCPA | California Privacy Protection Agency | Bloomberg: CCPA & CPRA
Contamination of early CDC COVID-19 tests in 2020 > CDC distributed flawed test kits Feb 6, 2020 - contaminated reagents caused false positives > 24 of 26 public health labs found contamination, CDC recalled kits by Feb 10 > Tests made in CDC lab (not manufacturing facility), violated sound manufacturing practices > Contamination occurred in Respiratory Virus Diagnostic Lab during processing > — NPR: CDC Test Flawed | CNN: CDC Contamination > Note: Delays had significant consequences for early pandemic tracking and response
Cellular Turnover and Repair Rates in the Human Body > 330 billion cells replaced daily (~1% of all cells, 3.8 million/second) > 80 grams of cellular mass turnover per day, dominated by blood cells (86%) and gut epithelial cells (12%) > Complete body cell replacement in 80-100 days (average cell age: 7 years) > — Scientific American: Body Replaces Billions of Cells | Weizmann: Cell Replacement Numbers > Note: Despite constant regeneration, we age due to DNA mutations that accumulate as cells replicate > Produce 2 million red blood cells per second > Generate new stomach lining every 3-5 days > Replace your entire skin every 28 days (surface cells every 2-4 weeks) > Rebuild your skeleton every 10 years > — HowStuffWorks: Body Replace Every 7 Years | Live Science: Cell Replacement | Sanitas: Body Regeneration
FDA regulations for charging for investigational drugs (21 CFR 312.8) > Sponsors may charge for investigational drugs under expanded access with prior FDA authorization > Can recover direct costs (manufacturing, shipping) + monitoring/admin costs for treatment INDs > Must not interfere with drug development for marketing approval > Authorization valid for 1 year; requires independent CPA review of cost calculations > — 21 CFR 312.8 | FDA Guidance: Charging for Investigational Drugs > Note: Allows cost recovery but not profit; ensures patients can access investigational drugs while development continues
Chan Zuckerberg Initiative Funding/Pledge > Zuckerberg & Chan pledged 99% of Facebook stock worth ~$45 billion (2015) > Structured as LLC (not traditional foundation) to enable investments, policy advocacy > Started with $1 billion/year in Facebook stock for first 3 years > Focus: personalized learning, curing disease, connecting people, building communities > — Washington Post: Zuckerberg $45B Pledge | Philanthropy: CZI Pledge > Note: One of largest-ever philanthropic commitments, announced with birth of daughter Max in Dec 2015
Chance of dying from terrorism statistic > Chance of American dying in foreign-born terrorist attack: 1 in 3.6 million per year (1975-2015) > Including 9/11 deaths; annual murder rate is 253x higher than terrorism death rate > More likely to die from lightning strike than foreign terrorism > — Cato Institute: Terrorism and Immigration Risk Analysis | NBC News: Lightning vs Terrorism > Note: Comprehensive 41-year study shows terrorism risk is extremely low compared to everyday dangers
Global population percentage of children > Children ages 0-14: 24.73% of global population (2024) > Children under 18: ~2.415 billion globally (2023-2024) > Regional variation: >40% in Sub-Saharan Africa, 10-13% in aging populations (Japan, South Korea) > — World Bank: Population Ages 0-14 | UNICEF: Children in the World > Note: Share declining globally due to aging populations; projected ~24% (1.97B) by 2025
Childhood Vaccination (US) ROI > “Economic analysis for 2009 alone found that each dollar invested in vaccines saved more than $10 in total societal costs” > “In a 2005 study on the economic impact of routine childhood immunization in the United States, researchers estimated that for every dollar spent, the vaccination program saved more than $5 in direct costs and approximately $11 in additional costs to society.” > — CDC, Link | Vaxopedia, Link
China’s health/medical share of R&D > China’s total R&D: 2.23% of GDP (2019), 2.68% of GDP (2024) > Total health expenditure: 6.5% of GDP (2021), reached 7.6 trillion yuan > Pharmaceutical R&D: $150B (2019) → $342B (2023 forecast) > Life sciences priority area but specific health R&D percentage not publicly reported > — UNESCO: R&D Spending by Country | PMC: China Health Expenditure Analysis | Statista: China Pharma R&D
China’s medical research spending (2024): ~$15 billion > Total R&D spending: 3.6 trillion yuan (~$500B USD, 2024), 2.68% of GDP > Basic research: 249.7 billion yuan (~$35B), 6.91% of total R&D (10.5% increase from 2023) > Life sciences is priority area alongside quantum tech, materials science, space > China is world’s 2nd largest R&D spender after US ($784B vs $723B in 2023) > — China National Statistics: R&D 2024 | Global Times: China R&D Growth > Note: Specific health/medical research breakdown not publicly reported; life sciences receives increasing investment
Cost of China’s military parades > 2015 Victory Day (70th anniversary): 12,000 PLA troops, 1,000 foreign troops, 850,000 “Citizen Guards” > 2025 parade estimated >36 billion yuan ($5 billion, ~1.5% of defense budget) - Taiwan estimate > Beijing rarely discloses parade costs; estimates cannot be independently verified > — Wikipedia: 2015 China Victory Day Parade | NBC News: 2025 China Parade Cost > Note: Massive mobilization for propaganda purposes; costs remain state secret
China spending on surveillance vs. medicine > Domestic security/surveillance: ~1.45 trillion yuan (2023) > Healthcare (public expenditure): ~2.24 trillion yuan (2023) > Domestic security spending first exceeded defense budget in 2010 > 2017: ~$197B domestic security ($349B PPP basis), more than double US’s $165B > — Nikkei Asia: China Public Security | Jamestown: China Domestic Security Analysis > Note: While healthcare receives more total funding, domestic security spending has tripled in past decade, emphasizing internal stability control
China’s total R&D spending > 2024: 3.6130 trillion yuan ($495-500B USD), up 8.3% from 2023 > R&D intensity: 2.68% of GDP (2024) > Basic research: 249.7 billion yuan (~$35B), 6.91% of total R&D, 10.5% increase from 2023 > World’s 2nd largest R&D spender after US ($784B vs China’s $500B in 2024) > — China National Statistics: R&D 2024 | Global Times: China R&D $495B | Statista: China R&D Spending
Chinese vs. American researcher salary comparison > China average: ¥275K-300K (~$38K-43K USD); Elite: ¥800K+ (~$110K-120K+) > US average: $89K-130K; Many positions $130K-209K > Gap: American scientists earn 2-3x more on average > Entry-level in China: ¥7K/month (~$12K annually) at government institutes > — PayScale: China Research Scientist | Glassdoor: US Research Scientist > Note: Gap narrowing for elite Chinese scientists at top universities; “The gap is vanishing” - Tsinghua senior scientist
Survey on American adults’ knowledge of agriculture > 7% of Americans (16.4 million) reportedly believe chocolate milk comes from brown cows > 48% said they don’t know where chocolate milk comes from > Survey methodology heavily criticized - responses: “brown cows, black-and-white cows, or didn’t know” (no correct option given!) > — Washington Post: Chocolate Milk Survey | CJR: Survey Analysis > Note: Innovation Center for U.S. Dairy survey not publicly available; question wording didn’t include correct answer as option. 55% incorrect/don’t know strains credulity
Winston Churchill quote on democracy > Democracy is the worst form of government, except for all the others. > — UK Parliament, Hansard, November 11, 1947 | International Churchill Society, The Worst Form of Government | Full quote: “Indeed, it has been said that democracy is the worst form of Government except all those other forms that have been tried from time to time”
Impact of Citizens United Supreme Court decision on campaign finance > Citizens United v. FEC (2010): 5-4 Supreme Court decision allowing unlimited corporate/union political spending > Overruled restrictions on independent expenditures, citing First Amendment > Led to creation of super PACs and massive increases in dark money > Dramatically expanded influence of wealthy donors, corporations, special interest groups > — Citizens United v. FEC, 558 U.S. 310 | Brennan Center: Citizens United Explained > Note: Overwhelming majorities of Americans disapprove; 22+ states voted to support constitutional amendment to overturn
Survey of American civic literacy (Congress’s function) > 64% can’t name or describe three branches of government > Only 25% can name all three branches (down from 38% in 2011) > 27% know 2/3 vote needed to override veto > 70%+ fail basic civic literacy quiz > — Annenberg: Americans’ Civic Knowledge | US Chamber Foundation: Civic Literacy Study > Note: Elected officials score worse (44%) than general public (49%). 54% of elected officials don’t know Congress has power to declare war
Survey of American civic literacy (naming representatives) > Only 37% of Americans can name their Representative > 23% who voted for Representative can’t name who they voted for > Most can’t name US Senators > Yet 65% believe their Representative is overpaid > — Haven Insights: Name Your Representative | MRCTV: Only 37% Can Name Congressman > Note: Voters who can’t name representatives still have strong opinions about their performance and compensation
Clean Water & Sanitation (LMICs) ROI > “For every dollar invested in water and sanitation, there is a $4.3 return in the form of reduced health care costs for individuals and society around the world” > “Universal access to clean water, toilets, and hygiene would boost the global economy by trillions of dollars over the next two decades… and would bring returns of 21 times their cost.” > — UN News, Link | WaterAid, Link
Climate Bonds: GSS+ debt $5.5T cumulative > “By the end of 2023, Climate Bonds had recorded USD5.5tn of cumulative GSS and SLB (collectively GSS+) volume, of which USD4.4tn (80%) was found to be aligned.” > — Climate Bonds Initiative, 2024, State of the Market
Cost breakdown of traditional clinical trials > Median clinical trial cost: $19.0 million (range: $12.2M - $33.1M) > Cost per patient varies by phase: Phase 1: ~$137K, Phase 2: ~$130K, Phase 3: ~$113K > — JAMA Internal Medicine: Clinical Trial Costs Study > Note: Based on analysis of 138 clinical trials. Actual costs can vary significantly based on disease area, trial complexity, and patient population
Clinical trial enrollment timelines > “Today nearly 80% of clinical trials fail to meet their enrolment timelines and up to 50% of research sites enrol one or no patients. > Not only does this translate into as much as $8m in lost revenue for each day a drug is delayed, it also means that cutting-edge new medications are significantly delayed in their journey to the patients who need them most.” > — Clinical Trials Arena, Link
Clinical trial patient participation rate > Only 3-5% of adult cancer patients in US receive treatment within clinical trials > About 5% of American adults have ever participated in any clinical trial > Oncology: 2-3% of all oncology patients participate > Contrast: 50-60% enrollment for pediatric cancer trials (<15 years old) > — ACS CAN: Barriers to Clinical Trial Enrollment | HINTS: Clinical Trial Participation > Note: ~20% of cancer trials fail due to insufficient enrollment; 11% of research sites enroll zero patients
$61 billion global annual clinical trial expenditure > “The global clinical trials market size was valued at USD 60.94 billion in 2024. > The market is projected to grow from USD 64.94 billion in 2025 to USD 104.41 billion by 2032…” > “The global clinical trials market accounted for USD 59 billion in 2024. > The market is anticipated to grow from USD 62.4 billion in 2025 to USD 98.9 billion in 2034…” > — Fortune Business Insights, May 2024 | Global Market Insights, Feb 2024
CMS Innovation Center (CMMI) Overview > “The Innovation Center tests innovative payment and service delivery models to reduce expenditures.” > — CMS, CMMI Overview
Cognitive Limit in Short-Term Memory (Miller’s Law) > Short-term memory capacity: 7 ± 2 items (Miller’s Law) > The “magical number seven” - humans can hold approximately 7 chunks of information in working memory > — George A. Miller, 1956, The Magical Number Seven, Plus or Minus Two: Some Limits on Our Capacity for Processing Information, Psychological Review, Vol. 63, No. 2 > Note: This classic psychology paper has been cited over 40,000 times and fundamentally shaped our understanding of human cognitive limitations
Percentage of time members of Congress spend fundraising > Recommended: 4 hours “call time” + 1 hour “strategic outreach” = 5 hours/day out of 9-10 hour workday > New members told to spend 30 hours/week on fundraising calls since Citizens United > Tom Daschle: ~67% of schedule is money-gathering in 2 years before election > Only 3-4 hours/day for actual Congressional work (hearings, votes, constituents) > — CBS 60 Minutes: Congressional Telemarketers | HuffPost: Call Time > Note: By law, members cannot fundraise from offices; parties set up call centers near Capitol
Congress adding funds to defense budget not requested by the Pentagon > FY2025: $15 billion unrequested for hundreds of military programs > FY2023: $61.4 billion for all categories of military spending (not requested) > FY2022: $58 billion worth of military projects (not requested) > Past 4 years: >$100 billion for 2,000+ weapons programs (no public debate) > — Military.com: $15B Unrequested Weapons | Roll Call: $100B+ Unrequested Since 2022 > Note: Bipartisan phenomenon; most additions <$30M but add up substantially
Congressional committee assignments have explicit fundraising price tags > DCCC (Democratic): Speaker $31 million, “A” Committee Chairs $1.8 million, Regular members $150,000 minimum > NRCC (Republican): Speaker $20 million, Power Committee Chairs $1.2 million, Transportation Chair $875,000 > Members display “giant tally sheet” showing who has/hasn’t paid their party dues > Members who don’t pay dues get bills killed, amendments ignored, worse offices > Rep. Brett Guthrie: Paid $2.5 million (53% of campaign funds) for Energy & Commerce Chair > Rep. Rosa DeLauro: Paid $690,000 (39% of campaign funds) for Appropriations > — Issue One: The Price of Power | The Intercept: DCCC Committee Dues | Brookings: Committee Tax in Congress | Roll Call: Committee Gavels Don’t Come Cheap > Note: System criticized as “recipe for corruption” disconnecting members from constituents
Salary of a U.S. Congressman > Members of Congress: $174,000/year (2009-present) > Speaker of the House: $223,500/year > Majority/Minority Leaders: $193,400/year > — U.S. Senate: Salaries | Congressional Research Service Report > Note: Congressional salary has been frozen at $174,000 since 2009, unchanged for over 15 years
Conscious mind controls ~5% of decisions > Conscious of only ~5% of cognitive activity; 95% is unconscious/subconscious > Brain signals predict decisions up to 7 seconds before conscious awareness > 90% of buying decisions made subconsciously > “Most of what we do every minute is unconscious” - neuroscientist Paul Whelan > — ScienceDaily: Unconscious Decision Making | PMC: The Unconscious Mind > Note: All decisions made unconsciously first, then we “fool ourselves” into believing we consciously made them
Defense Contracts (2001-2021) > “The top five defense firms received $2.02 trillion in contracts from the Pentagon during the 20 years of the war in Afghanistan.” > — Responsible Statecraft, 2021, Top defense firms see $2T return on $1B investment in Afghan war
Children’s Online Privacy Protection Act (COPPA) > Federal law effective April 21, 2000; applies to websites/services collecting data from children under 13 > Requirements: Privacy policy; Verifiable parental consent before collecting data; Data security; Parental review/deletion rights > Applies to: For-profit businesses collecting personal info from US children under 13 > Penalties: Up to $50,120 per violation > Enforcement: FTC and State Attorneys General > — FTC: COPPA Rule | Wikipedia: COPPA | eCFR: 16 CFR Part 312
Corporate lobbying spending in 2023 > Federal lobbying: $4.26 billion (2023 record high), up from $4.11B (2022) > Combined federal + state: $5.6 billion > Top industry: Pharmaceuticals/health products ($379M) > Top spender: US Chamber of Commerce ($69.6M) > — Statista: Total Lobbying Spending 2023 | OpenSecrets: Federal Lobbying > Note: National Association of Realtors #2 at $52M; lobbying spending continues breaking records
How campaign contributions influence politicians > Research: Only 1 in 4 studies support notion that contributions directly “buy votes” > Influence mechanism: Access, agenda-setting, keeping bills off floor, earmarks, key language in legislation (not direct votes) > Average winner costs (2022): House $2.79M, Senate $26.53M; Competitive races much higher > Internal party fundraising requirements: $100K-$30M annually; Committee positions cost $450K > 95% of House races since 2004 won by highest spender > Contribution limits: $3,300 per candidate per election (individuals); PACs gave $289.3M total (2021-2022) > — ScienceDirect: Campaign Contributions & Legislative Behavior | Slate: Cost to Buy a Vote | OpenSecrets: Cost of Election | Issue One: Congressional Fundraising
Estimated cost of providing universal healthcare globally > New investments needed: $104B/year initially → $274B/year by 2030 ($41/person) > 85% can be met with domestic resources in most countries > 32 poorest countries face $54B annual gap, need external assistance > Current gap: 4.5 billion people not fully covered (2021) > — WHO: Cost of Reaching Global Health Targets by 2030 | WHO: UHC Fact Sheet > Note: Would prevent 97M premature deaths 2017-2030, add 8.4 years life expectancy in some countries
Costa Rica abolished its army in 1949 > December 1, 1948: José Figueres Ferrer declared abolition of armed forces > October 31, 1949: Constitutional abolition codified in Article 12 > First country to constitutionally abolish its military > Figueres symbolically broke wall with mallet to end military’s existence > — UNESCO Memory of the World: Abolition of Army | Wikipedia: Article 12 Costa Rica Constitution > Note: Budget redirected to security, education, culture. 14 countries followed; 28 nations now have no armies
Comparison of U.S. deaths from COVID-19 vs. major wars > COVID-19 US deaths: 1.2+ million total (as of 2024) > WWII: 405,000 | Korea: 36,000 | Vietnam: 58,000 = 499,000 combined > By March 2021: COVID deaths (527,726) exceeded WWI, WWII, Vietnam, 9/11 combined > By Oct 2021: 704,233 deaths exceeded ALL US foreign conflict deaths (~685,000 total) > — Statista: COVID vs War Deaths | Snopes: COVID vs Foreign Conflicts > Note: COVID killed more Americans than Revolutionary War, War of 1812, WWI, WWII, Korea, Vietnam, and other conflicts combined
Economic Damage of COVID-19 Pandemic > Total cost: $16 trillion (~90% of US annual GDP) > Lost GDP output: $7.6 trillion | Premature deaths: $4.4T | Long-term health: $2.6T | Mental health: $1.6T > Loss is 4x greater than Great Recession > More than 2x total cost of all US wars since 9/11 (Afghanistan, Iraq, Syria) > — JAMA: The $16 Trillion Virus | Harvard Gazette: COVID Cost > Note: Estimate by David Cutler & Lawrence Summers (Harvard); separate study found $14T by end of 2023
Current median household wealth of ~$100,000 > Median household net worth: $192,084 (2023) / $187,690 (2024 adjusted) > Census: $176,500 (2022) up from $120,000 (2016) - 61% increase > 60% of US households have net worth $100K+ > 29.2% have net worth $500K+ > — DQYDJ: Net Worth Percentiles | Census: Home Equity & Net Worth > Note: Growth driven by home values, stock market gains, pandemic savings. Median nearly doubled since 2016
Cybercrime economy projected to reach $10.5 trillion > Global cybercrime costs: $3T (2015) → $6T (2021) → $10.5T (2025 projected) > 15% annual growth rate > If measured as country, would be 3rd largest economy after US and China > Greatest transfer of economic wealth in history > — Cybersecurity Ventures: $10.5T Cybercrime | Boise State: Cybercrime Costs > Note: More profitable than global trade of all major illegal drugs combined. Includes data theft, productivity loss, IP theft, fraud
96% of cybercrimes go unpunished > Less than 1% of cybercrimes prosecuted (UK: 65 prosecutions vs 17,900 reported cases in 2018) > ~99% of cybercrimes go unpunished > Perpetrators extremely difficult to identify and pursue > Cross-national boundaries make prosecution nearly impossible > — CSO Online: Why Internet Crime Goes Unpunished | Information Security Buzz: 1% Prosecuted > Note: Rules of evidence and international jurisdiction make cybercrime possibly harder to prosecute than any other area of law enforcement
Daily death toll statistics by geographic region > South Asia | 45,000 | 29,000 > East Asia | 38,000 | 17,000 > Sub-Saharan Africa | 35,000 | 26,000 > Europe | 16,000 | 5,000 > North America | 8,000 | 2,000 > Latin America | 8,000 | 4,000 > — PMC: Heart of the World - CVD Regional Burden | Lancet: CVD in Americas > Note: North America ~900K-1M CVD deaths/year; Latin America/Caribbean >1M deaths/year (2021)
DAO multisig vulnerabilities to technical and social exploits > Technical exploits: The DAO hack (2016) stole 3.6M ETH ($60M) via reentrancy attack; vulnerabilities include DoS, gas limits, overflow/underflow, 51% attacks > Social engineering: Multiple pseudonyms to control multisig wallets, impersonation, malware emails, fake job offers; exploit humans when code vulnerabilities diminish > Multisig issues: Many DAOs use ⅔ multisig (too low, easily exploitable); attackers can hold multiple positions to meet quorum > Governance risks: Brief voting windows, uncritical proposal review allow malicious proposals > — Quorum: Auditing Social Layer of DAO | BlockScience: DAO Vulnerabilities | Consensys: State of DAO Security
Death Causes vs Fear (Heart Disease vs Terrorism) > Cardiovascular disease: 19.2-20.5 million deaths annually (2023 data) > Terrorism: approximately 25,000 deaths per year > CVD accounts for 1 in 3 global deaths - the leading cause for over 30 years > — IHME: CVD Deaths 2023 | World Heart Federation Report 2023 > Note: CVD deaths increased 60% from 12.1M (1990) to 20.5M (2021). 4 in 5 CVD deaths occur in low- and middle-income countries
Annual deaths from treatable diseases > 15.6 million excess deaths in low/middle-income countries from 61 conditions > 8.6 million amenable to health care: 5.0M from poor-quality care + 3.6M from non-utilization > WHO Europe: 1.8M avoidable NCD deaths/year (preventable or treatable) > 39 million deaths could be averted by 2030 with proven interventions > — PMC: Mortality Due to Low-Quality Health Systems | WHO: Avoidable NCD Deaths > Note: 17M people <70 die prematurely from NCDs annually; biggest killers: CVD, cancer, respiratory, diabetes
Assets Under Management by Defense Contractor Pension Funds > Defense contractors collectively: ~$100 billion in pension assets > Lockheed Martin alone: $17.7B pension funding gap (mid-2018) > Pension costs to DOD grew from <$500M (2002) to ~$5B (2011) > Major contractors among largest defined benefit plan sponsors in US > — Pensions & Investments: Defense Contractor Pension Assets | GAO: Pension Costs on DOD Contracts > Note: Lockheed transferred $4.3B in pension obligations in 2022. Taxpayers fund much of these contractor pensions
Salary comparison between defense industry and NIH > Raytheon engineers: ~$121K average ($97K-161K range) > NIH Research Scientists: ~$209K average ($166K-269K range) > NIH Staff Scientists: ~$115K average ($137K-224K range) > Entry-level comparison: NIH PhDs $75K-100K vs Raytheon engineers ~$85K-120K > — Glassdoor: Raytheon Salaries | Glassdoor: NIH Salaries > Note: Senior NIH positions generally pay more; defense contractors have “terrible compensation” vs tech companies
Delaware has more corporate entities than residents > Delaware population: <1 million residents > Business entities: 1.6 million+ (2020) - 2:1 ratio over residents > 2019: 1.5 million entities vs <1M people > 66% of Fortune 500 incorporated in Delaware > 93% of US IPOs are Delaware entities > — Delaware Division of Corporations: 2020 Annual Report | Princeton Press: What’s the Matter with Delaware? > Note: 249,427 new business entities added in 2020 alone. Unique 2:1 corporation-to-resident ratio
Depression is the leading cause of disability worldwide > “Depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease.” (WHO, 2017) > Depression is the leading cause of disability as measured by Years Lived with Disability (YLDs) > Fourth leading contributor to the global burden of disease (DALYs) > More than 300 million people living with depression (18% increase 2005-2015) > — WHO: Depression Let’s Talk (2017) | UN News: Leading Cause of Disability | JAMA: Depression Leading Cause
Global prevalence of depression: 280 million > 280 million people worldwide have depression (2019 WHO) > Includes 5% of all adults, 5.7% of adults 60+ > 23 million children and adolescents affected > More common among women than men > — WHO: Depression Fact Sheet | Our World in Data: Mental Health > Note: 75%+ in low/middle-income countries receive no treatment. In 2021, 1.1B lived with mental disorder globally
dFDA ROI of 463:1 over 10 years > NPV analysis estimate: 463:1 ROI over 10 years (central estimate) > Range: 66:1 to 2,577:1 depending on total ecosystem costs > Based on: $37.5-46M upfront platform investment + operational costs vs $50B annual R&D savings > Value proposition: 80X reduction in per-patient trial costs; $50B gross annual savings from pharma R&D > Pharmaceutical industry spends ~$100B/year on R&D; 50% cost reduction yields enormous net savings > — dFDA: Cost Benefit Analysis | dFDA Wiki
Annual deaths from diabetes > Diabetes | 2M deaths/year > — International Diabetes Federation, 2024, IDF Diabetes Atlas | WHO, 2021, Diabetes Fact Sheet | Note: 3.4 million deaths in 2024 (IDF), including direct and indirect deaths from diabetes complications
Lobbying spending and returns for disease advocacy groups > Each $1,000 spent on lobbying correlated with $25,000 funding increase following year (53 diseases, 19 years) > Rare disease advocates increased NIH rare-disease funding 3-15%/year (1998-2008) via millions in lobbying > Specific examples: Alzheimer’s Association secured $100M NIH increase (FY2024); ME/CFS Initiative helped secure >$1B for long-COVID > General ratio: Disease advocacy lobbying yields significant ROI, though specific “$100M → $1.8B” not verified > — NYU Stern: Lobbying Influences NIH Funding | Nature: Lobbying Sways NIH Grants | Alzheimer’s Association: $100M Increase
Global disease burden as a percentage of global GDP > Poor health reduces global GDP by 15% annually (McKinsey Global Institute) > Impact from: premature deaths + lost productive potential in working-age population > ~2X the pandemic’s negative impact in 2020 > 70% of economic benefits achievable via: cleaner/safer environments, healthier behaviors, vaccines/preventive medicine > Additional burden: NCDs (CVD, respiratory, cancer, diabetes, mental health) = $47T cumulative output loss over 2 decades (75% of 2010 global GDP) > — McKinsey: Poor Health Reduces GDP 15% | WEF: Global Economic Burden of NCDs
Annual global economic burden of Alzheimer’s and other dementias > Global cost: $1.3 trillion (2019 WHO-commissioned study) > 50% from informal caregivers (family/friends, ~5 hrs/day) > 74% of costs in high-income countries despite 61% of patients in LMICs > $818B (2010) → $1T (2018) → $1.3T (2019) - rapid growth > — WHO: Dementia Fact Sheet | Alzheimer’s & Dementia: Worldwide Costs 2019 > Note: Costs increased 35% from 2010-2015 alone. Informal care represents massive hidden economic burden
Annual global economic burden of cancer > 2020-2050 projection: $25.2 trillion total ($840B/year average) > 2010 annual cost: $1.16 trillion (direct costs only) > Recent estimate: ~$3 trillion/year (all costs included) > Top 5 cancers: lung (15.4%), colon/rectum (10.9%), breast (7.7%), liver (6.5%), leukemia (6.3%) > — JAMA Oncology: Global Cost 2020-2050 | Nature: $25T Over 30 Years > Note: China/US account for 45% of global burden; 75% of deaths in LMICs but only 50% of economic cost
Annual global economic burden of diabetes > 2015: $1.3 trillion (1.8% of global GDP) > 2030 projections: $2.1T-2.5T depending on scenario > IDF health expenditure: $760B (2019) → $845B (2045 projected) > 2/3 direct medical costs ($857B), 1/3 indirect costs (lost productivity) > — Diabetes Care: Global Economic Burden | Lancet: Diabetes Economic Burden > Note: Costs growing rapidly; expected to exceed $2T by 2030
Annual global economic burden of heart disease > Heart failure alone: $108 billion/year (2012 global analysis, 197 countries) > US CVD: $555B (2016) → projected $1.8T by 2050 > LMICs total CVD loss: $3.7T cumulative (2011-2015, 5-year period) > CVD is costliest disease category in most developed nations > — Int’l Journal of Cardiology: Global Heart Failure Burden | AHA: US CVD Costs to 2050 > Note: No single $2.1T global figure found; estimates vary widely by scope and year
Annual global economic burden of kidney disease > Inside CKD study (31 countries): $372B (2022) → $407B (2027) > CKD pre-KRT: ~$202B (2022) → ~$220B (2027) > Kidney replacement therapy: ~$187B (2027) despite only 5.3% of CKD patients > US alone: $162B (2022) → $173B (2027) > — PMC: Inside CKD Global Economic Burden | Lancet eClinicalMedicine: CKD Projections > Note: $600B figure not found; $372-407B for 31 countries represents most comprehensive global estimate. KRT alone costs ~$187B
Annual global economic burden of mental illness > 2010: $1.3T → 2019 dollars: $1.6T (DALYs valued at 1x GDP per capita) > Depression/anxiety alone: $1T/year in lost productivity (WHO) > Total direct + indirect: $2.5T (2010 data: $0.8T direct, $1.7T indirect) > Updated 2019 estimate: ~$5T economic value of mental disorder burden > Projected 2030: $16T cumulative global cost > — PMC: Economic Costs of Mental Disorders | eClinicalMedicine: Quantifying Mental Disorder Burden > Note: Depression/anxiety productivity losses forecast to hit $16T by 2030. Indirect costs (lost productivity) exceed direct treatment costs 2:1
Annual global economic burden of respiratory diseases > EU-28 (2019): €380 billion (~$420B) annually for chronic respiratory disease care > Global burden: 454.6M prevalent cases, 4M deaths annually (2019) > COPD: 212.3M cases, 3.3M deaths (primary mortality driver) > Asthma: 262.4M cases (highest prevalence) > US worker costs (2011-2015): $7B asthma + $5B COPD annually > — Lancet Respiratory Medicine: GBD 2017 CRDs | Frontiers in Medicine: CRD Burden 2019 | CDC MMWR: US Worker Costs > Note: €380B EU figure is partial global estimate. Third leading cause of death globally from chronic respiratory diseases
$109 trillion annual global disease burden > “The global economic burden of disease, including direct healthcare costs ($8.2 trillion) and lost productivity ($100.9 trillion from 2.55 billion DALYs × $39,570 per DALY), totals approximately $109.1 trillion annually.” > — Calculated from IHME Global Burden of Disease (2.55B DALYs) and global GDP per capita valuation | See detailed calculation: Cost of Disease Analysis
Global prevalence of chronic disease > 2.3 billion individuals had more than five ailments (2013) > Chronic conditions caused 74% of all deaths worldwide (2019), up from 67% (2010) > Approximately 1 in 3 adults suffer from multiple chronic conditions (MCCs) > Risk factor exposures: 2B exposed to biomass fuel, 1B to air pollution, 1B smokers > Projected economic cost: $47 trillion by 2030 > — ScienceDaily: GBD 2015 Study | PMC: Burden of Chronic Disease | PMC: Multiple Chronic Conditions > Note: 2.3B with 5+ ailments is more accurate than “2B with chronic disease.” One-third of all adults globally have multiple chronic conditions
Number of diseases cured since 2014 > Hepatitis C: Interferon-free treatments approved Nov 2013/Jan 2014 (FDA/EMA) > DAAs can cure >95% of HCV patients in 8-12 weeks > HCV is the only chronic viral illness that can be completely cured > Since then: No other chronic diseases have achieved “cure” status > — PMC: Hepatitis C Elimination | Military Medical Research: HCV to Clinical Cure | WHO: Hepatitis C Fact Sheet > Note: Hepatitis C represents unprecedented achievement - from discovery (1989) to cure in ~25 years. Remains the fastest viral disease ever identified and cured
36:1 disparity ratio of spending on weapons over cures > Global military spending: $2.7 trillion (2024, SIPRI) > Global government medical research: ~$68 billion (2024) > Actual ratio: 39.7:1 in favor of weapons over medical research > Military R&D alone: ~$85B (2004 data, 10% of global R&D) > Military spending increases crowd out health: 1% ↑ military = 0.62% ↓ health spending > — SIPRI: Military Spending | PMC: Military vs Healthcare Crowding Out | Congress.gov: Global R&D Landscape > Note: Ratio actually worse than 36:1. Each 1% increase in military spending reduces health spending by 0.62%, with effect more intense in poorer countries (0.962% reduction)
DOT Value of Statistical Life ($13.6M) > Current VSL (2024): $13.7 million (updated from $13.6M) > Used in cost-benefit analyses for transportation regulations and infrastructure > Methodology updated in 2013 guidance, adjusted annually for inflation and real income > VSL represents aggregate willingness to pay for safety improvements that reduce fatalities by one > — DOT: VSL Guidance 2024 | DOT: Economic Values Used in Analysis > Note: DOT has published VSL guidance periodically since 1993. Current $13.7M reflects 2024 inflation/income adjustments
Drug development success rate: 0.01% > Preclinical to approval: 0.003-0.005% (1 in 20,000-30,000 compounds) > Phase I to approval: 6.7-12.8% (recent decline from historical ~10%) > Average likelihood of approval (LOA): 14.3% for Phase I (range 8-23% by company) > 75-80% of failures due to efficacy/safety problems > — PMC: Approval Success Rates | PMC: Why 90% Fail | ScienceDirect: Benchmarking R&D Success 2006-2022 > Note: 0.01% figure is slightly high for preclinical compounds (actual 0.003-0.005%), but approximately correct order of magnitude. Success rate from Phase I is ~10-15%
Drug Price Competition and Patent Term Restoration Act of 1984 > Also known as: Hatch-Waxman Act (Public Law 98-417) > Signed by Reagan: September 24, 1984 > Sponsors: Rep. Henry Waxman (CA) and Sen. Orrin Hatch (UT) > Created modern generic drug regulation system via Abbreviated New Drug Applications (ANDAs) > Patent term extension: Up to 5 years (max 14 years total from approval) > Generic incentive: 180 days market exclusivity for first paragraph IV certification > 5-year data exclusivity for new chemical entities > — Wikipedia: Hatch-Waxman Act | Congress.gov: H.R.3605 | CRS: Hatch-Waxman Primer > Note: Landmark legislation balancing generic access with innovation incentives. Generic manufacturers only need to show bioequivalence, not repeat clinical trials
Drug trial success rate from Phase I to approval > Overall Phase I to approval: 10-12.8% (conventional wisdom ~10%, studies show 12.8%) > Recent decline: Average LOA now 6.7% for Phase I (2014-2023 data) > Leading pharma companies: 14.3% average LOA (range 8-23%) > Varies by therapeutic area: Oncology 3.4%, CNS/cardiovascular lowest at Phase III > Phase-specific success: Phase I 47-54%, Phase II 28-34%, Phase III 55-70% > — Nature Reviews Drug Discovery: Clinical Success Rates | PMC: Estimating Success Rates | Oxford Academic: Clinical Trial Success > Note: 12% figure accurate for historical average. Recent data shows decline to 6.7%, with Phase II as primary attrition point (28% success)
Decentralized Trials & Research Alliance (DTRA) > 501(c)(3) nonprofit organization (US) > Launched: December 10, 2020 by Dr. Amir Kalali and Craig Lipset (co-chairs) > Membership: 100+ organizations by Jan 2021 (pharma, biotech, academic, FDA, VA) > Mission: Make research participation accessible; accelerate adoption of patient-focused, decentralized clinical trials > Emerged during COVID-19 to address slow adoption of decentralized methodologies > — DTRA Official Site | Wikipedia: DTRA | VA News: Decentralized Trials > Note: COVID-19 pandemic forced rapid adoption of decentralized trial methods. DTRA provides forum for stakeholder collaboration to maintain momentum
Education investment economic multiplier (2.1) > Early childhood education: Benefits 12X outlays by 2050; $8.70 per dollar over lifetime > Educational facilities: $1 spent → $1.50 economic returns > Energy efficiency comparison: 2-to-1 benefit-to-cost ratio (McKinsey) > Private return to schooling: ~9% per additional year (World Bank meta-analysis) > — EPI: Public Investments Outside Core Infrastructure | World Bank: Returns to Investment in Education | Freopp: Education ROI Framework > Note: 2.1 multiplier aligns with benefit-to-cost ratios for educational infrastructure/energy efficiency. Early childhood education shows much higher returns (12X by 2050)
Environmental cost of war ($100B annually) > War on Terror emissions: 1.2B metric tons GHG (equivalent to 257M cars/year) > Military: 5.5% of global GHG emissions (2X aviation + shipping combined) > US DoD: World’s single largest institutional oil consumer, 47th largest emitter if nation > Cleanup costs: $500B+ for military contaminated sites > Gaza war environmental damage: $56.4B; landmine clearance: $34.6B expected > Climate finance gap: Rich nations spend 30X more on military than climate finance > — Brown Watson Costs of War: Environmental Cost | Earth.Org: Environmental Impact of Wars | Transform Defence: Military Spending & Climate > Note: Military activities cause massive environmental damage through GHG emissions, toxic contamination, and long-term cleanup costs far exceeding current climate finance commitments
Executive Order 13944 (2020) on Essential Medicines > Full title: “Combating Public Health Emergencies and Strengthening National Security by Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs Are Made in the United States” > Signed by Trump: August 6, 2020 > Goal: Establish resilient domestic supply chains for essential medicines/APIs > Required “Produced in the United States” including Active Pharmaceutical Ingredients (APIs) > Authorized Defense Production Act use to prioritize domestic contracts > FDA published list of essential medicines: October 30, 2020 > — Trump White House Archives: EO 13944 | Federal Register: EO 13944 | FDA: EO 13944 List > Note: Response to COVID-19 revealed US dependence on foreign pharmaceutical manufacturing. Order aimed to reduce vulnerability to supply chain disruptions
Executive Order 14158 (DOGE) > “Establishing and Implementing the President’s Department of Government Efficiency.” > — White House, 2025, EO 14158
Executive Order 14210 (DOGE Workforce Optimization) > “Implementing the President’s Department of Government Efficiency, Workforce Optimization Initiative.” > — White House, 2025, EO 14210
Executive Order 14222 (DOGE Cost Efficiency) > “Implementing the President’s Department of Government Efficiency, Cost Efficiency Initiative.” > — White House, 2025, EO 14222
EPA Value of Statistical Life ($9.6M) > EPA 2010 Guidelines: $7.9M (2008 dollars) → ~$9.7M (2013 dollars/income adjusted) > Current EPA VSL: ~$10 million (highest among federal agencies) > Based on 1997 Clean Air Act analysis; updated for inflation/income but not methodology > Uses wage-risk literature (21 studies) and stated preference studies (5 studies) > Used in cost-benefit analyses for environmental, health, and safety regulations > — EPA: Mortality Risk Valuation | RFF: Revisiting EPA’s VSL | EPA: VSL White Paper > Note: $9.6-9.7M represents EPA’s VSL with inflation/income adjustments. Base methodology hasn’t been updated since 1997
Erectile dysfunction drug market size: $3 billion/year > 2024: $2.92-3.27 billion (varies by source) > 2030 projected: $4.90-6.81 billion > Viagra (sildenafil): 57.3% market share (2024) > Viagra patent expired 2020; Pfizer launched generic at $65 (50% off brand) > North America: 50.55% of global market (2024) > Leading players: Pfizer, Eli Lilly (Cialis), Teva, Sanofi, Bayer > — Grand View Research: ED Drugs Market | Cognitive Market Research: ED Drug Market | Precedence Research: ED Market to 2034 > Note: $3B figure accurate for 2024. Market growing rapidly (9-9.2% CAGR) due to aging populations and reduced stigma
Estonia e-Residency statistics > “Estonia’s e-Residency program has issued digital identities to over 100,000 people from 170+ countries, demonstrating global-scale digital identity verification.” > — e-Residency, 2024, Statistics
Estonia’s digital governance model > KSI Blockchain introduced: 2012 (first application: Succession Registry) > Three technological pillars: e-ID (2002), X-Road (2001), KSI Blockchain (2012) > KSI = Keyless Signature Infrastructure (built by Guardtime) > Used by NATO and US Department of Defense > 99% of state operations can be done digitally (except marriage, divorce, real estate) > Applications: health records, school systems, e-ID, taxation, property registries, online voting > — e-Estonia: KSI Blockchain | Medium: Estonia’s Blockchain Success | Oxford Academic: Blockchain at Government Level > Note: KSI is timestamp system preserving document integrity - only hash values sent to blockchain, original data never leaves servers
Estonia internet voting lessons > “Estonia’s i-Voting enables secure, anonymous online voting worldwide using e-ID, enhancing citizen participation in governance.” > — Academic and official analyses, e.g., e-estonia.com
Estonia’s X-Road blockchain-based health system > X-Road developed: 2001; blockchain integration: 2008 > Backbone of governmental and private services connecting different information systems > Security: All incoming data authenticated/logged; outgoing data digitally signed/encrypted on KSI > Scales to 10^12 items per second > Health records: 99% digitalized, 100% patients have digital records > EHR integrates data from all healthcare providers into common record patients access online > Patients can track medical visits and monitor who accessed their records in real-time > — e-Estonia: Estonian e-Health Records | Invest in Estonia: e-Health | GovInsider: Estonia Blockchain Health Records > Note: X-Road provides interoperability and security layer. KSI blockchain (added 2011) ensures integrity of medical records and access logs. System demonstrates full transparency - patients see all access
EU Compassionate Use program for experimental drugs > Established by: Article 83 of Regulation (EC) No 726/2004 > Eligibility: Life-threatening, long-lasting, or seriously debilitating illnesses > Requires: No satisfactory authorized treatment; medicine in trials or approval process > EMA role: CHMP provides recommendations; national authorities implement programs > Pan-European programs rare: Only 6 approved by EMA in last 10 years vs hundreds of national programs > Each EU member state sets own rules and procedures > — EMA: Compassionate Use | PMC: Overview of Compassionate Use in EU | EURORDIS: Early Access to Promising Medicines > Note: Pan-European framework exists but rarely used due to complex navigation across varying national regulations. Most programs remain country-specific
EU eIDAS network for electronic identification > eIDAS = Electronic IDentification, Authentication and trust Services > Regulation (EU) No 910/2014 - establishes framework for digital identity/authentication > Mutual recognition: Member states must recognize each other’s national eID schemes > Interoperability: Technology-neutral framework enabling seamless cross-border authentication > Levels of Assurance (LoA): Low, substantial, or high confidence in identification > eIDAS 2.0: Introduces European Digital Identity Wallets (EUDI Wallets) - standardized throughout EU > Citizens/businesses can use eIDs from one member state to access services in another > — EU Digital Strategy: eIDAS Regulation | EUR-Lex: Regulation 910/2014 | Wikipedia: eIDAS > Note: eIDAS 2.0 enhances original framework with digital identity wallets operating seamlessly across all EU member states. Crucial for secure cross-border electronic transactions
Horizon Europe Health Budget (2021-2027): €8.2 billion > Horizon Europe total budget: €95.5 billion (2021-2027) > Cluster 1 “Health”: €8.246 billion dedicated to health research > Alternative figures: €7.7B (some sources) or €8.3B (including Next Generation EU: +€1.1B) > Managed by: Health and Digital Executive Agency (HaDEA) > Pillars structure: Cluster 1 Health falls under Pillar 2 (Global Challenges) > — HRB: Horizon Europe Health Information | HaDEA: Horizon Europe Health | Health-NCP-Net: Horizon Europe > Note: Most consistent official figure is €8.246B for Cluster 1 Health. Variations reflect different components or inclusion of Next Generation EU supplemental funds
EU MiCA transparency and disclosure > “MiCA establishes uniform requirements for the offer to the public and admission to trading of crypto‑assets… and for transparency and disclosure.” > — EUR‑Lex, 2023, MiCA Regulation
Average drug approval timeline in Europe > EMA assessment: Up to 210 ‘active’ days; total ~1 year with clock-stops > Development (first human testing to approval): 8-10 years standard; 5-7 years with expedited programs > FDA vs EMA: FDA approves 95% of new oncology drugs first; median EU delay: 227-241 days > FDA review time: 8.7 months vs EMA: 15.5 months > — EMA: From Lab to Patient Timeline | PMC: FDA vs EMA Cancer Therapy Timings | Value in Health: US vs EU Authorization Timelines > Note: 5-7 year timeline refers to expedited development programs from first human trials to approval. Standard is 8-10 years. EMA assessment itself takes ~1 year, but FDA typically approves first with 7-8 month median lead time
Evolutionary Mismatch and Modern Disease > “Many modern diseases result from a mismatch between our evolutionary adaptations and current environments, particularly regarding diet and physical activity.” > — Lieberman, Daniel, 2013, The Story of the Human Body: Evolution, Health, and Disease
Estimated excess deaths attributed to FDA’s COVID-19 response > FDA regulations restricted clinician/patient access to COVID-19 testing, remdesivir, vaccines > General drug delay estimate: 37,000-76,000 deaths per one-year delay > Testing delays: By May 2020, 400+ applications awaiting FDA review > Seattle lab ordered to stop testing Feb 16 for lack of FDA approval > Gates Foundation partnership instructed to discontinue testing May 2020 until authorization > EUA process prevented months of vaccine/testing delays > — PMC: EUAs vs FDA Approval Implications | PMC: FDA & COVID Political Economy | Yale Law Journal: Deadly Delay FDA Role > Note: Specific “500,000+” figure not found in sources. Research shows FDA testing restrictions caused weeks-to-months of critical delays (Feb-March 2020). One-year drug delay = 37-76K deaths
Executive Orders on Regulatory Reform > Trump EO 13771 (2017): “2 for 1” - Repeal 2 regulations for every new one; eliminated 5.5:1 actual ratio > Trump EO “Unleashing Prosperity Through Deregulation” (Jan 31, 2025): “10 for 1” - Repeal 10 for every new one > Trump EO (Feb 19, 2025): Agencies identify regulations for rescission/modification > Requirement: Total incremental cost of new FY2025 regulations “significantly less than zero” > Biden: Rescinded EO 13771 (Jan 20, 2021); revised OMB Circular A-4 (2023) for evidence-based analysis > Trump (2025): Revoked Biden’s 2023 A-4 revision > — Wikipedia: EO 13771 | White House: 10-to-1 Deregulation | Skadden: Rolling Back Administrative State > Note: Multiple administrations pursued regulatory reform. Massive existing regulatory costs (trillions) remain unchecked; new rules represent small fraction of total burden
F-35 cost compared to global rare disease research funding > Single F-35 cost: $82M (flyaway) to $110-136M (with ancillary costs) > NIH rare disease funding (FY2023): $6.9 billion (world’s largest public biomedical research funder) > NIH rare disease funding = <0.1% of NIH’s $48B annual budget > Comparison: ~63 F-35s = 1 year of US rare disease research funding > F-35 total program cost: $2.1 trillion lifetime (2,456 aircraft through 2088) > — Responsible Statecraft: F-35 Cost $2T | Statista: Rare Diseases Funding NIH | Arms Control Center: F-35 Costs & Challenges > Note: One F-35 ($110-136M) doesn’t exceed annual rare disease funding ($6.9B), but claim illustrates stark military vs medical research disparity. 63 F-35s = entire year of rare disease research
F-35 program cost details and manufacturing locations > Gen 3 HMDS helmet: $400,000 (Rockwell Collins/Elbit Systems) > Helmet total cost for all F-35s: $1 billion+ > Features: 360° camera view, night vision, custom-fitted (2 days), targeting system > Suppliers: 1,650-1,900+ suppliers across 49 states and Puerto Rico > Jobs: 290,000+ US jobs supported > Economic impact: $72 billion into US economy annually > International: 10+ countries have suppliers > — New Atlas: $400K Helmet | Air Force Times: F-35 Helmet | POGO: F-35 and Captured State > Note: Helmet more expensive than Ferrari. Distributed manufacturing across 49 states = political protection for program. Each state has jobs dependent on F-35 continuation
F-35 program lifetime cost: $1.7 trillion > F-35 Program lifetime cost: $2.1 trillion (updated April 2024) > Sustainment costs: $1.58 trillion (44% increase from 2018 estimate) > Procurement costs: $422 billion > Covers 94 years of operation (through 2088) for 2,456 aircraft > — GAO: F-35 Sustainment Costs | Breaking Defense: F-35 Lifetime Cost > Note: About half the cost increase is due to inflation. This makes the F-35 one of the most expensive military acquisition programs in modern history
Average annual new drug approvals by FDA > FDA approved 55 new drugs in 2023 (average of 53 per year over last 5 years) > 56% were Priority Review, 36% were first-in-class, 51% were orphan drugs > 84% approved on first-cycle review > — FDA: New Drug Therapy Approvals 2023 | PMC: FDA Drug Approvals 2023 > Note: 2023 was the second-best year for approvals after 2018 (59 approvals). Monoclonal antibodies had exceptional year with 12 approvals
FDA drug approval timeline > Full timeline (preclinical to market): 12-15 years average (10-15 years common range) > Preclinical phase: 3-7 years > Clinical development + NDA review: ~9 years > NDA review alone: 10 months average (standard); 6 months (priority review) > Historical (pre-PDUFA): 21-29 months for NDA review > — Drugs.com: FDA Drug Approval Process | FDAReview.org: Drug Development & Approval | PMC: Drugs, Devices, FDA Overview > Note: “10 years” is accurate for total development timeline (10-15 year range). Modern FDA review is faster (10 months) thanks to PDUFA, but overall timeline remains 12-15 years
Total number of FDA-approved drugs > FDA approves ~50-55 new drugs annually (2023: 55; 5-year avg: 53) > Cumulative total not specified in search results > DrugBank database tracks all approved drugs globally > Estimate: Several thousand including different formulations/dosages > — PMC: FDA Drug Approvals 2023 | Statista: CDER Drug Approvals 2008-2023 | DrugBank: Statistics > Note: Specific “~5,000” total not confirmed in sources. Annual approval rate: 50-55 new molecular entities. Total includes variations of same drug (different doses/formulations)
FDA FY24 Budget Request for Modernization > FY2024 total request: $7.2 billion (+$372M increase in discretionary authority) > Food safety & nutrition modernization: $128.2M (includes food labeling, oversight) > IT modernization across agency: Part of broader digital transformation initiative > Devices Program: Digital Transformation initiative funding > Biologics: Information management & data infrastructure modernization > Outdated IT processes modernization across all programs > — FDA: FY2024 Budget Summary | FDA: FY24 CJ Online Version > Note: Specific “$105M for modernization” not found. $128.2M for food safety modernization; broader IT modernization across multiple programs. Total FY24 request: $7.2B
FDA delay in approving rapid COVID-19 tests > Feb 16, 2020: Seattle research lab ordered to stop COVID testing without FDA approval > May 2020: Gates Foundation partnership instructed to discontinue testing until authorization > Feb 29, 2020: U. Nebraska finally got FDA permission after Feb 4 special permission > Timeline: Critical delays measured in weeks-to-months (Feb-March 2020), not specific “6 months” > FDA guidance suggested EUAs needed for laboratory-developed tests (LDTs), causing delays > By May 2020: 400+ test applications awaiting FDA review > — CNN: How Government Delayed Testing | Yale Law Journal: Deadly Delay | HHS OIG: FDA EUA Adaptations > Note: Delays were weeks-to-months during critical Feb-March 2020 period, not continuous “6 months.” FDA intervention added minimal value while contributing to deadly delays
FDA Cure-ID Program > Free platform developed by FDA & NIH (NCATS) to share off-label drug uses/repurposing > Focus: 325 difficult-to-treat infectious diseases (neglected tropical, AMR organisms, emerging threats) > Allows healthcare providers to report new uses via standardized case report form (web/mobile) > Mission: Generate real-world evidence for off-label drugs with high public health impact, low commercial viability > Providers can browse documented cases, treatment results, relevant clinical trials > Expansion: Automating EHR data extraction; adding anonymized registry data > Access: https://cure.ncats.io | App/Play Store > — CURE ID: About | C-Path: CDRC and CURE ID FAQs | FDA: CURE ID Automated Data Collection > Note: Platform exists and functions. “Insufficient Incentives and Network Effects” may refer to adoption challenges, but platform provides real-world evidence infrastructure
Estimated deaths from FDA drug lag (1962-present) > Dale Gieringer (1985): 21,000-120,000 lives lost per decade from FDA delay > Gieringer: “Loss of life from delay alone in the hundreds of thousands” (not millions) > Beta-blockers alone: William Wardell estimated “10,000 lives/year” if allowed; FDA delay 1965-1976 > Sam Peltzman: Post-1962 death toll from regulatory delay “easily number in thousands per year” > Practolol (beta-blocker): “Could save 10,000 lives/year” (Wardell estimate) > FDA allowed propranolol 1968 (3 years after Europe); for hypertension/angina not until 1978 > — FEE: Patients and Doctors vs FDA | Econlib: Drug Lag | FDAReview.org: Theory, Evidence, Examples of FDA Harm > Note: “4-10 million” figure not found in sources. Gieringer’s estimates: 21K-120K deaths per decade, “hundreds of thousands” total (not millions). Specific drug delays (beta-blockers): ~100K deaths estimated
FDA mandate pre-1962 focused on safety, not efficacy > Pre-1962: 1938 Food, Drug and Cosmetic Act required only that drugs be safe for use > FDA regulated safety only, not efficacy before 1962 > 1962 Kefauver-Harris Amendment: Added efficacy requirement after thalidomide tragedy > JFK signed amendment: October 10, 1962 > Post-1962: FDA requires “adequate and well-controlled investigations” proving both safety AND efficacy > Also added: Informed consent requirement, adverse event reporting to FDA > — Wikipedia: Kefauver-Harris Amendment | FDA: Promoting Safe & Effective Drugs 100 Years | PMC: Kefauver-Harris Amendments at 50 > Note: 1962 amendment fundamentally changed FDA from safety-only to safety-and-efficacy regulator, laying groundwork for phased clinical trial system we have today
FDA Mandate to Accelerate Innovation (21 U.S.C. § 393(b)(2)(B)) > 21 U.S.C. § 393(b) - FDA statutory mission includes advancing regulatory science, promoting innovation > Section 1124 of Public Law 112-144 (July 9, 2012): FDA must develop strategy for advancing regulatory science for medical products > Goal: “Promote public health and advance innovation in regulatory decisionmaking” > Mandate: Foster collaboration between FDA, NIH, other science-based Federal agencies > Purpose: Enhance FDA’s scientific/technical expertise for drug development, clinical investigation, evaluation, post-market monitoring > — 21 U.S.C. § 393 | Public Law 112-144 (FDASIA 2012) > Note: Statutory mandate exists to promote innovation, but implementation and prioritization remain subject to FDA discretion and resource allocation
Evidence of FDA regulatory capture by pharmaceutical industry > FY2023: User fees = 75% of PDUFA program costs (vs 7% in FY1993) > FY2022: User fees = 66% ($1.4B) of human drugs program budget > FY2022: User fees = 46% ($2.9B) of FDA’s total $6.2B budget > Pharma finances ~75% of FDA’s drug division (New York Times) > Concerns: Budgetary dependence, urgency of PDUFA reauthorizations, required industry participation in negotiations > Most PDUFA policy changes favor industry: decreased regulatory standards, shorter approval times, increased industry involvement > FDA maintains decisions based on science, not fee collection ability > — CRS: FDA Human Medical Product User Fees | ASPE: FDA User Fees Issue Brief | PMC: PDUFA - More Than User Fees > Note: Regulatory capture concerns well-documented. Industry funding grew from 7% (1993) to 75% (2023) of drug review program. No evidence found for “10x government salary” claim for FDA reviewers
Number of key FDA drug reviewers > CDER review teams: ~1,300 employees evaluate and approve new drugs > CDER safety team: 72 employees monitor 3,000+ prescription drugs for 200 million people ($15M/year budget) > FDA Advisory Committees (all 3 centers): ~300 individuals serve on ~40 committees > Advisory committees stable in recent years > — Wikipedia: Center for Drug Evaluation and Research | NCBI: FDA Advisory Committee System > Note: “~200” may refer to advisory committee members (~300 actual) or be approximation. CDER has 1,300 review staff total. Safety monitoring: 72 people for 200M patients
FDA Sentinel Initiative > Launched: May 2008 in response to FDAAA 2007; transitioned to full system Feb 2016 > Purpose: Active post-market risk identification and analysis (ARIA) for medical products > Scale: World’s largest multisite distributed database for medical product safety; 128.7M members > Data sources: Insurance claims, electronic health records, patient reports > Privacy: Distributed data approach - data remains with owners, patient identifiers removed > Structure (2019): 3 coordinating centers - Operations, Innovation, Community Building/Outreach > Real-World Evidence: RWE Data Enterprise (RWE-DE) - 25.5M lives (21M commercial + 4.5M academic) > 2008-2014: FDA mandated 657 studies under FDAAA authority > — FDA: Sentinel Initiative | PMC: Sentinel - Learning Health System | Wikipedia: Sentinel Initiative > Note: Major advancement in post-market surveillance. “Limited Transparency and Bureaucratic Constraints” may refer to challenges, but system represents significant FDA capability improvement
FDA clinical trial launch timeline > IND application: FDA has 30 days to object or allow trials to begin > NDA/BLA preparation after Phase 3: 6-12 months to assemble safety/effectiveness data > Standard NDA review: ~10-12 months median (standard review) > Priority review: 6 months (vs 10 months standard) > Overall development (first human testing to approval): 12-15 years full timeline > Expedited programs: 7.1 years median vs 8.0 years nonexpedited > — FDA: IND Application Procedures | Drugs.com: FDA Approval Process | PMC: FDA’s Expedited Programs 2012-2016 > Note: “6-12 months” likely refers to NDA/BLA preparation time post-Phase 3, not total trial launch timeline. IND review: 30 days. Full approval timeline: 10-15 years
FDA trial patient exclusion criteria > Most frequent exclusions: Pregnancy, lactation/breastfeeding, renal/hepatic abnormalities, specific infectious diseases > Pregnant/lactating women: >90% of trials exclude > Older adults: ~27% exclude based on age (arbitrary upper limits) > Patients with organ dysfunction: Excluded due to adverse impact concerns from comorbidities/concomitant meds > Multiple chronic conditions: Often exclusion criterion despite being common in target population > Children/adolescents: Excluded due to ethical considerations > High-risk patients: Prior malignancy history, active brain metastases, suboptimal hepatic/renal function, HIV+ > FDA guidance: Working to broaden eligibility; “exclusions based on age alone rarely appropriate” > — FDA: Evaluating Inclusion & Exclusion Criteria | ScienceDirect: Eligibility Criteria FDA Perspective | ASCO: Transforming Eligibility Criteria > Note: Exclusion criteria often eliminate patients who would actually use the drug, reducing real-world applicability of trial results
Paperwork comparison between FDA trials and RECOVERY trial > RECOVERY trial paperwork: One-page consent form, one-page case report form, single follow-up form > Randomisation form: Simple, collecting few baseline characteristics and ensuring eligibility > Follow-up: Single form completed at earliest of discharge, death, or 28 days > Eligibility criteria: Simple; trial processes (including paperwork) minimized > Philosophy: “Avoid additional burden on busy clinicians, so trial procedures streamlined as far as possible” > FDA Form 1572: Statement of Investigator form required for IND trials (specific form, not total page count) > — PMC: Making Trials Part of Good Clinical Care - RECOVERY | PMC: Establishing COVID-19 Trials at Scale - RECOVERY | FDA: Form 1572 > Note: Specific “1,572 pages vs 24 pages” comparison not found in sources. RECOVERY used 1-page forms. FDA Form 1572 is a specific required form, not total paperwork count. RECOVERY’s streamlined approach demonstrated feasibility of simplified trial documentation
FDA Amendments Act (FDAAA) of 2007 > Signed by: President George W. Bush, September 27, 2007 > Key provisions: Population-based surveillance system (Sentinel), post-approval study authority, REMS > Risk Evaluation and Mitigation Strategies (REMS): Medication guides, communication plans, patient registries > Post-market studies: FDA can require studies/trials after approval; monetary penalties for noncompliance > ClinicalTrials.gov: Required registration of all clinical trials; summary results within 12 months of completion > Medical devices: Added pediatric use category; allowed >36 month surveillance for devices with pediatric use > 2008-2014: FDA mandated 657 studies under FDAAA authority > — Wikipedia: FDAAA 2007 | NEJM: FDAAA Effects a Decade Later | Congress.gov: H.R.3580 > Note: Major expansion of FDA authority. Introduced Sentinel Initiative mandate. Significantly improved FDA’s capacity to track medication effects and mitigate risk post-approval
FDA Modernization Act of 1997 (FDAMA) > Signed by: President Bill Clinton, November 21, 1997; fully enacted April 1, 1999 > Fast Track Approval: Section 112 - expedited study/approval based on clinical or surrogate endpoints > Single study sufficient: One clinical study may provide adequate efficacy data for all products > Post-approval requirements: Fast track drugs subject to Phase IV studies after approval > PDUFA reauthorization: Extended for 5 years; helped FDA hire 600+ employees, cut approval time in half (30→15 months) > Patient access: Codified FDA practice to increase access to experimental drugs/devices > Medical devices: Focused FDA resources on highest-risk devices > Biologics: Modernized regulation, harmonized with drug regulations, eliminated establishment license application need > Other: Pediatric drug studies, pharmacy compounding exemptions, expanded health claims for food labeling > — Wikipedia: FDAMA 1997 | Congress.gov: S.830 | GovInfo: Public Law 105-115 > Note: Significant streamlining of FDA processes. Cut drug approval time in half. Expanded access to experimental treatments. Laid groundwork for modern expedited approval pathways
FDA Safety and Innovation Act (FDASIA) of 2012 > Signed by: President Obama, July 9, 2012 > Reauthorized: PDUFA V, MDUFA III > GDUFA: Authorized FDA to collect $299M/year (adjusted for inflation) in generic drug review fees > Breakthrough Therapy Designation: Section 902 - expedited development/review for drugs showing substantial improvement over existing therapies; 60-day review > Drug shortages: Prevention and mitigation provisions > Drug supply chain safety: New authorities (Title VII) for increasingly global supply chain > Other: Priority review vouchers for rare pediatric diseases, enhanced device innovation, patient engagement in development > — FDA: FDASIA | Wikipedia: FDASIA | PMC: User Fees and Beyond - FDASIA 2012 > Note: Introduced Breakthrough Therapy designation (60-day review). Authorized generic drug user fees for first time. Major advancement in expedited pathways
FEC Foreign National Restrictions > “A foreign national shall not, directly or indirectly, make a contribution or a donation of money or other thing of value, or expressly or impliedly promise to make a contribution or a donation, in connection with any Federal, State, or local election.” > — 52 U.S.C. § 30121(a)(1)(A), FEC Guidelines
FEC Foreign Nationals Guidance > “The Federal Election Campaign Act (FECA) prohibits any foreign national from contributing, donating or spending funds in connection with any federal, state or local election in the United States, either directly or indirectly.” > — Federal Election Commission, Foreign Nationals
FECA violation penalties > Civil (not knowing/willful): Greater of $6,500 or amount involved > Knowing/willful (conduit contributions): Greater of $55,000 or 1,000% of amount > Criminal threshold: Conduit contributions >$10K = up to 2 years; >$25K = up to 5 years > Notable case: $250,000 fine for foreign contributions (one of highest on record) > Foreign national enhancement: +2 levels (foreign government: +4 levels) > — Wiley: FEC Increases Civil Penalties | USSC: Amendment 648 | Inside Political Law: Criminal Campaign Finance > Note: Penalties vary widely. Criminal prosecution requires “knowing and willful” violation. Foreign national involvement triggers enhanced penalties reflecting seriousness of foreign election interference
Fast Healthcare Interoperability Resources (FHIR) Standard > Developed by: HL7 (Health Level 7); presented May 2012; evolved through 4 releases to 145 resources > Purpose: API-focused standard for exchanging healthcare information electronically > Core: Modular “Resources” - generic definitions (patient, observation, practitioner, device, condition) > Technical: RESTful APIs using HTTP requests; combines advantages of HL7 v2, v3, CDA > Adoption: Steadily rising since 2010, peaked 2021; enables connected health ecosystem > Benefits: Strengthens interoperability, supports innovative applications, improves health outcomes > — HL7: FHIR Overview | Wikipedia: FHIR | HealthIT.gov: HL7 FHIR > Note: FHIR is the modern standard replacing older HL7 formats. Enables patient records to be available, discoverable, understandable across healthcare ecosystem
Food Abundance in Modern Society > “The average American has access to approximately 3,800 calories per day in the food supply, nearly double the recommended daily intake.” > — USDA Economic Research Service, 2019, Food Availability and Consumption
Fossil Fuel Lobbying ROI > “The fossil fuel industry spends millions on lobbying and gets billions in subsidies – an ROI of over 800%.” > — The Guardian, 2021, Fossil fuel lobbying ROI
Fossil Fuel Subsidies ($7T, 2022) > “Fossil fuel subsidies surged to a record $7 trillion last year as governments supported consumers and businesses during the global spike in energy prices caused by Russia’s invasion of Ukraine and the economic recovery from the pandemic.” > — IMF, 2023, Fossil Fuel Subsidies Surged to Record $7 Trillion
France medical research spending: ~$4 billion/year > Health Innovation Plan 2030 (June 2021): €7.5B total investment > Biomedical research allocation: >€1B specifically for biomedical research > Cross-cutting support: €1B for clusters, translational research, attracting scientists, R&D infrastructure > Technology maturation/clinical trials: €500M > Industrial investments: €1.5B; Startups (Bpifrance): €2.1B > Broader R&D goal: Raise spending from 2.2% to 3% of GDP; public spending €15B → €20B by 2030 > — French Healthcare: Health Innovation Plan 2030 | Campus France: France 2030 Boost Health Research > Note: €7.5B Health Innovation Plan includes >€1B for biomedical research specifically. Total health research spending higher when including broader categories
Federal Trade Commission Act (15 U.S.C. § 45) > 15 U.S.C. § 45: “Unfair methods of competition in or affecting commerce, and unfair or deceptive acts or practices in or affecting commerce, are hereby declared unlawful” > FTC authority: Issue complaints, conduct hearings, prevent unfair/deceptive practices in public interest > Civil penalties (2023): $50,120 per violation for Section 5 violations > Exemptions: Banks, savings & loans, Federal credit unions, common carriers, air carriers, entities under Packers & Stockyards Act > Foreign commerce: Includes acts causing/likely to cause reasonably foreseeable injury in US or involving material conduct in US > — 15 U.S.C. § 45 | Federal Register: Civil Penalty Adjustments 2023 > Note: Broad FTC authority to address unfair and deceptive business practices. $50K+ per violation enables substantial penalties for widespread violations
Deaths from furniture accidents compared to terrorism > Since 9/11/2001: Americans no more likely to die from terrorism than being crushed by unstable TVs/furniture > Furniture tip-over fatalities (2000-present): 581 total; 4 in 5 deaths were children > 2013-2023: 217 reported tip-over fatalities (23% TV, 25% TV+furniture, 46% furniture only, 7% appliance) > Comparison: Even in Israel (intensive terror campaign), weekly terror casualties almost never match traffic deaths > US terrorism: Deaths so low they barely register on graphs except 9/11/2001 > — Washington Post: More Likely Crushed by Furniture | CPSC: Tip-Over Report 2023 | Our World in Data: Terrorism vs Other Causes > Note: Post-9/11, furniture tip-overs have caused comparable/greater fatalities than terrorism for Americans. Highlights media attention vs actual risk disparity
Gates Foundation Endowment Size > Current (July 31, 2025): $86 billion (unaudited); Dec 31, 2024: $77.2 billion > 2022: ~$70 billion (with new gifts added) > Total contributions: Bill & Melinda Gates $60.2B (inception-2024); Warren Buffett $43.3B (2006-2024) > Structure: Gates Foundation Trust manages endowment; Gates Foundation conducts operations/grantmaking > World’s largest private philanthropic foundation > Intent: Spend endowment “down to zero” within 20 years of Bill & Melinda’s deaths > Annual payout (2026): $9B/year (50% increase announced 2022) > — Gates Foundation: Fact Sheet | Fortune: Spend Down to Zero > Note: $70B figure accurate for 2022. Endowment has since grown to $86B (July 2025). Dramatic growth from major contributions by Gates + Buffett
GDP of China > 2024 nominal GDP: RMB 134.91 trillion ≈ US$18.80 trillion > Growth: 5.0% year-on-year (met “around 5%” target); Q4 accelerated to 5.4% > Global rank: 2nd largest economy (US #1 at ~$29T projected 2024) > Global contribution: ~30% of global economic growth annually in recent years > — China Briefing: China’s Economy 2024 | Wikipedia: Economy of China | Visual Capitalist: China’s $18.6T Economy > Note: China’s GDP is ~$18.8 trillion (2024). Second largest economy globally after US (~$29T)
Gross Domestic Product (GDP) of Greenland > 2023 GDP: $3.33 billion USD (World Bank official data) > 2021 GDP: >20 billion Danish kroner > Economy: Heavily dependent on fishing exports and Danish government subsidies > Danish subsidy (2017): ~$535M budgeted (>50% of government revenues, 25% of GDP) > — Trading Economics: Greenland GDP | Wikipedia: Economy of Greenland | World Bank: Greenland Data > Note: Greenland’s economy is tiny at $3.3 billion, heavily subsidized by Denmark. Useful for scale comparisons
GDPR Biometric Data requirements > “Processing of biometric data for the purpose of uniquely identifying a natural person shall be prohibited unless one of the conditions referred to in points (a) to (j) of paragraph 2 applies.” > — GDPR Article 9(1), EU General Data Protection Regulation
Generic Drug User Fee Act (GDUFA) > First authorized: 2012 (FDASIA); renewed 5-year cycles: GDUFA II (2017), GDUFA III (2022) > Authorizes FDA to collect fees for: ANDAs, DMFs, API facilities, FDF facilities, CMO facilities, applicant programs > FY2026 rates: ANDA ($358K), DMF ($103K), domestic FDF facility ($239K), foreign FDF ($254K), large applicant program ($1.9M) > ANDA fees: 33% of total fee revenue > Program fee: Annual fee for firms sponsoring approved ANDAs (not per-ANDA) > DMF fee: One-time fee when first referenced in generic drug submission > — FDA: GDUFA | CRS: Generic Drug User Fee Amendments | Federal Register: GDUFA Rates FY2026 > Note: First generic drug user fees (2012). Provides additional FDA revenue for generic drug review. Established performance goals for application review times
General Dynamics annual revenue > 2024 revenue: $47.7 billion (12.9% increase from 2023) > 2022 revenue: $39.407 billion (matches “$39B” claim) > 2024 net earnings: $3.8 billion (up 14.1% from 2023) > Backlog: $90.6 billion; Total estimated contract value: $144 billion > Products/services: Business aviation, ship construction/repair, land combat vehicles, weapons systems/munitions, technology > HQ: Reston, Virginia > — General Dynamics: Q4 & FY2024 Results | Statista: General Dynamics Revenue > Note: $39B figure accurate for 2022. Current 2024 revenue is $47.7B, reflecting significant growth in defense contractor spending
Generic Drug Substitution Savings > “According to the IMS Health Institute, generic drugs saved the U.S. health care system $1.67 trillion from 2007 to 2016.” > — FDA, Link
Survey on Americans’ geographic literacy > National Geographic-Roper 2002 Survey (18-24 year-olds, 9 countries): US next-to-last > 11% of young Americans couldn’t locate US on map > Pacific Ocean: 29% couldn’t find; Japan: 58%; France: 65%; UK: 69% > <50% could identify New York or Ohio on US map > European Union knowledge: 2 in 5 Americans don’t know which countries in EU > 18-26 college attendees: Average 55% on geography/current events/economics test (failing grade) > US consistently scores near bottom vs peers in developed nations > — National Geographic: Survey Reveals Geographic Illiteracy | National Geographic-Roper 2006 Report | ETIAS: EU Country Survey > Note: Severe geographic illiteracy documented across multiple surveys. Specific “can’t find Europe on map” not found, but 65% couldn’t find France, 69% couldn’t find UK
Germany medical research spending: ~$6 billion/year > 10-year plan (Dec 2020): Raise R&D from 2.2% to 3% of GDP; public spending €15B → €20B by 2030 > Research funding system: Federal Ministry of Education & Research (BMBF) + German Research Foundation (DFG) > Medical biotechnology: Strong industry sector with government support > Biomedical research investment: Significant portion of overall R&D budget > Public investment in biomedical research (Europe-wide context): Germany major contributor > — Research in Germany: Government Funding | Lancet: Public Investment in Biomedical Research Europe | Science: German Research Budget Increases > Note: Specific “$6 billion” for medical research not confirmed. Germany committed to raising total public R&D spending to €20B by 2030, with significant biomedical research component
Gitcoin Passport for digital identity scoring > Now: Human Passport (acquired by human.tech late 2024); >2M users > Purpose: Sybil resistance solution for web3, privacy-preserving identity verification > How it works: “Stamps” from web2/web3 identifiers (Twitter, Google, BrightID, Proof of Humanity) aggregated into unique identity score > Scoring: Weights based on “cost of forgery” and ability to signal unique humanity > Privacy: Verifiable credentials check identity without viewing PII > Customizable: Communities create custom “entry visa” with participation requirements > Use cases: Governance voting, gaming, airdrops, bot prevention > Gitcoin Grants Round 15: 35,000+ donors created Passports; limited Sybil activity, ensured fair fund distribution > — Gitcoin: Intro to Passport | Human Passport | Gitcoin: Building Sybil Resistance > Note: Leading web3 identity/Sybil resistance tool. Now operates as Human Passport after acquisition. Proven at scale with millions of users
GiveWell Cost per Life Saved for Top Charities (2024) > General range: $3,000-$5,500 per life saved (GiveWell top charities) > Helen Keller International (Vitamin A): $3,500 average (2022-2024); varies $1,000-$8,500 by country > Against Malaria Foundation: $5,500 per life saved > New Incentives (vaccination incentives): $4,500 per life saved > Malaria Consortium (seasonal malaria chemoprevention): ~$3,500 per life saved > VAS program details: ~$2 to provide vitamin A supplements to child for one year > — GiveWell: Top Charities | GiveWell: Helen Keller Vitamin A | Our World in Data: Cost-Effectiveness > Note: Figures accurate for 2024. Helen Keller VAS program has wide country variation ($1K-$8.5K) but $3,500 is accurate average. Among most cost-effective interventions globally
GiveWell Impact Multipliers > “Thus, if we estimate that a funding opportunity is ‘10x cash,’ this means we estimate it to be ten times as cost-effective as unconditional cash transfers.” > — GiveWell, 2023, Cost-Effectiveness
Global aging research spending: ~$500 million > NIH/NIA basic biology of aging (2019): $382 million (~1% of NIH budget) > NIA total budget (FY2020): $3.5 billion total, but ~$2.4B (60%) goes to Alzheimer’s (Neuroscience) > Geroscience/aging biology specifically: $382-500M annually from NIH system > Private sector: Hevolution Foundation pledged $1B annually; 2021: >$2B raised by longevity biotech (40+ deals) > Criticism: Aging research via NIA/NIH not properly funded relative to disease-specific research > — PMC: Funding Channels of Geroscience | NIA: FY2022 Budget | Spannr: Lack of Government Funding > Note: $500M figure accurate for public (NIH) geroscience/basic aging biology research. Majority of NIA’s $3.5B budget goes to Alzheimer’s, not fundamental aging research
Global armed forces size and average salary > Largest forces: China (2.0M active), India (1.4M), Russia (1.3M active, 3.5M total), US (1.3M active) > Global military spending 2024: US $1T (next 12 countries combined); NATO 32 members: $1.5T (55% of world) > Military spending per personnel: Tracked by SIPRI, World Bank (includes personnel, O&M, procurement, R&D, infrastructure, aid) > Average varies widely: US military much higher per-personnel spending than most countries > — Our World in Data: Military Personnel & Spending | World Bank: Armed Forces Personnel | SIPRI: Military Spending 2024 > Note: Specific “28.4M global armed forces” and “$24,000 average salary” not confirmed in sources. Data available but highly variable by country. Major forces total ~10M+ personnel among largest militaries
Global cancer research spending (~$51.4B, 2016-2023) > “Between 2016 and 2020, there was a total of US$24.5 billion of investment in public and charitable cancer research across 66,388 research grants globally… > The average annual spend over the years 2016-19 was US$5.5 billion per year.” > “A recent analysis covering 2016-2023 identified nearly 108,000 cancer research awards globally totaling $51.4 billion in government and philanthropic spending.” > “The U.S. National Cancer Institute’s fiscal year 2023 funds totaled $7.2 billion (including $216 million in Cures Act funding).” > — The Conversation, 2023, Billions spent on cancer research globally | The Lancet Oncology, 2023, Global funding for cancer research between 2016 and 2020 | NCI, 2024, Budget and Appropriations
Global cancer research spending > 2016-2020: $24.5 billion total (66,388 awards) in public/philanthropic funding > Annual average 2016-2019: $5.5 billion/year > 2016-2023: ~108,000 awards totaling $51.4 billion (government + philanthropic) > NCI FY2023: $7.2 billion (largest single funder globally) > Distribution by country (2016-2020): US 57.3% ($14.0B), UK 9.8%, EC 5.4%, China 4.4%, Japan 4.1% > Trend: Investment decreased each year 2016-2020 ($6.6B → $2.9B) > — Lancet Oncology: Global Funding 2016-2020 | NCI: Budget Fact Book | The Conversation: Billions Spent on Cancer Research > Note: “$20B/year” not accurate. Public/philanthropic funding averaged $5.5B/year (2016-2019). Does not include private pharmaceutical industry R&D which would increase total significantly
Global cancer research spending: ~$25 billion > 2016-2020 total: $24.5 billion (public + philanthropic); average $5.5B/year (2016-2019) > 2016-2023 total: $51.4 billion across ~108,000 awards > Annual estimates vary: $5.5B/year average (public/philanthropic only, 2016-2019) > NCI alone (FY2023): $7.2 billion > Does not include private pharmaceutical R&D which adds significantly to total > — Lancet Oncology: Global Funding 2016-2020 | The Conversation: Billions Spent Globally > Note: “$25B globally” could represent total including private pharma R&D, but public/philanthropic funding alone averaged $5.5B/year (2016-2019). $24.5B was 5-year total (2016-2020), not annual
Global cosmetics market size: $90 billion > 2024 market size: $311-420 billion (varies by source), NOT $90B > Fortune Business Insights: $335.95B (2024) > Straits Research: $311.23B (2024) > Precedence Research: $424.72B (2024); projected $760.61B by 2034 > Expert Market Research: $343.37B (2024) > IMARC Group: $419.8B (2024) > Projected growth: $354.68B (2025) → $556.21B (2032); CAGR 6.64% > — Fortune: Cosmetics Market | Precedence Research: Cosmetics Market | Oberlo: Global Cosmetics Market Size > Note: “$90B” is SIGNIFICANTLY understated. Actual 2024 market: $311-420B (3.5-4.7X higher than claimed)
Global dementia research spending (~$5-6B annually, 2024) > “In March 2024, bipartisan congressional leaders announced a $100 million increase for Alzheimer’s and dementia research funding at the National Institutes of Health (NIH) for fiscal year 2024, bringing the annual federal funding to as much as $3.8 billion.” > “Total G7 dementia research and development spending was nearly $800 million in 2012, with the United States being the largest funder of dementia research among the G7 countries.” > — Alzheimer’s Association, 2024, Congress Reaches Bipartisan Agreement on Alzheimer’s Research Funding | National Institute on Aging, Nations gather to coordinate global dementia research
Global disease burden savings of ~$9.76 trillion annually > NCDs total lost output (2011-2030): $47 trillion over 20 years = ~$2.35T/year > NCDs cost (2011-2030): >$30T (48% of 2010 global GDP); mental health alone: +$16.1T > 50% reduction potential savings example: TB 50% reduction = $900M cost, $6B saved, 16M deaths averted > — WEF: Global Economic Burden NCDs | PMC: Health Benefits Accelerated Research > Note: Specific “$9.76T annually from 50% reduction” not found in sources. NCD burden ~$2.35T/year average (2011-2030). 50% reduction would save roughly half, or ~$1.2T/year, not $9.76T
Global annual spending on education > 2022: $5.8-6.0 trillion globally > Morgan Stanley: $6T (2022) → $8T projected (2030); CAGR 4.4% > UNESCO GEM Report: $5.8T (2022); $4.7T (2019) > Distribution: 64% high-income countries, 0.45% low-income countries (despite equal school-age populations) > — Morgan Stanley: Global Education $8T Reboot | UNESCO: Finance GEM Report | HolonIQ: Global Education Market > Note: $6.0T figure accurate for 2022. Market growing to projected $8T by 2030. Highly concentrated in wealthy nations
Global annual spending on food > 2025: $9.37 trillion (worldwide food market revenue) > Growth: CAGR 6.34% (2025-2030); projected $12.37T by 2029 > 2022-2023: $6.73T → $7.22T (+7.3%) > Food & beverage industry (2024): >$12T globally (~11% of world GDP) > Food & grocery retail (2023): $11,932.5B (includes retail distribution) > — Statista: Food Market Revenue Worldwide | Statista: Food Worldwide Outlook | Gitnux: Global Food Industry Statistics > Note: $9.0T figure accurate for 2025 consumer food spending. Total food & beverage industry >$12T when including beverages and all channels
The Global Fund > “The Global Fund is a worldwide partnership to defeat HIV, TB and malaria and ensure a healthier, safer, more equitable future for all. > We raise and invest more than US$5 billion a year to fight the deadliest infectious diseases, challenge the injustice that fuels them and strengthen health systems in more than 100 of the world’s most affected countries.” > — The Global Fund, Overview
Lives saved by The Global Fund > 2025: 70 million lives saved (current figure) > Oct 2024: 65 million lives saved > Sep 2022: 50 million lives saved over 20 years > Death rate reduction: 63% combined death rate from AIDS, TB, malaria (61% since 2002) > Since inception (2002): Partnership saved 70M lives fighting HIV, TB, malaria across 100+ countries > — Global Fund: Results Report 2025 | Global Fund: 50M Lives Saved Press Release 2022 > Note: 50M was Sept 2022 figure. Current (2025): 70M lives saved. One of world’s most effective global health partnerships
Global GDP ($101T, 2022) > “The global economy is projected to grow from about 101 trillion U.S. dollars in 2022 to about 139 trillion U.S. dollars in 2027.” > — Statista, 2023, Global GDP
Global GDP in 2023 ($89.5 trillion) > “global GDP ($89.5 trillion in 2023)” > — World Bank, World GDP | Note: 2023 global GDP was $106.2T; 2024 was $111.3T according to World Bank data
Global GDP per capita ($12,263, 2022) > Global GDP per capita: $13,138 (2023), $12,263 (2022) > World GDP: $106.2 trillion (2023), $110.1 trillion (2024) > — World Bank, GDP per capita data | Statista: Global GDP per capita 2023 > Note: 2023 figures reflect continued global economic growth despite regional challenges
Global government medical research spending ($67.5B, 2023–2024) > “Global government spending on cure-oriented medical research reached approximately $67.5 billion in 2023–2024.” > — DFDA Wiki, 2025, Global Government Medical Research Spending
Global health spending as a share of GDP (9.8%, 2020) > “In 2020, global spending on health came to US$ 9 trillion, or 9.8% of global gross domestic product (GDP).” > — World Health Organization, Global Health Expenditure Report 2022
Global heart disease research spending: ~$8 billion > American Heart Association: >$6 billion funded total (largest private funder); current funding >$584M > NIH: 4% of budget on heart disease research, 1% stroke, 2% other CVD > US CVD healthcare spending (treatment, not research): $212B (1996) → $320B (2016) → $555B total (2016) > Projected costs by 2035: $1.1 trillion (treatment costs) > — AHA: Scientific Research | PMC: Spending on CVD in US 1996-2016 | ScienceDaily: CVD Costs $1T by 2035 > Note: “$8B globally” not confirmed in sources. AHA (largest private funder) has funded $6B+ total over all years, currently ~$584M/year. NIH allocates only 4% to heart disease research. Most figures found are treatment costs, not research
Global infectious diseases research spending: ~$12 billion > Global Fund: Raises/invests >$5B/year fighting HIV, TB, malaria in 100+ countries > Specific “$12B globally for infectious disease research” not confirmed in available sources > Related context: Most infectious disease funding reactive (after pandemics start) rather than proactive > — Global Fund: Overview > Note: “$12B” claim not verified. Global Fund alone invests >$5B/year on HIV/TB/malaria. Total global infectious disease research funding likely higher but specific figure not found
Global annual spending on infrastructure (roads & internet) > 2012: $4T; 2020: $4.2T; 2025 projected: $9T annually (PwC) > 2016: $3.1T actual spending > Investment needs 2016-2040: $94T total = $3.7T/year average needed > Investment gap: $4.5T/year needed - $2.5T/year shortfall = $18T total gap through 2040 (19% of forecast need) > Roads alone: $28T of global transport expenditure; roads represent >50% of infrastructure investment gap ($8T) > Spending must grow from 3% to 3.7% of global GDP to close gap > — MHI Spectra: Infrastructure Investment Doubling | Global Infrastructure Outlook | World Bank: $4.2T Saved by Resilient Infrastructure > Note: $4.0T figure accurate for 2012-2020 range. Current spending ~$3.1-4.2T/year but needs are $3.7T/year minimum, growing to $9T by 2025
Number of major global military facilities (4,435) > US military bases worldwide: 750-877 (varies by source/definition) > Conservative count: 128 military bases in 55 countries/territories (Feb 2025) > Broader count: 750+ bases in 80+ countries; some sources cite 877 > Large bases (>4 hectares or >$10M, >200 personnel): 439 (60% of US foreign bases) > Small bases/“Lily Pads” (<4 hectares or <$10M): Remaining 40% > Other nations: At least 18 other nations operate foreign military bases; NATO countries (France, UK): +200 locations > — Wikipedia: List of American Military Installations | Visual Capitalist: US Military Bases Overseas | World Beyond War: Military Empires > Note: “4,435” not found in sources. US operates 750-877 bases overseas. May include domestic + all nations’ bases combined, but specific figure not verified
Global mental health research spending > Global mental health research: $3.7 billion/year (Lancet Psychiatry 2020 analysis) > 2015-2019: 75,956 grants, $18.5B total = ~$3.7B/year > Represents 4% of all registered grants and 4% of total research investment > Geographic distribution: 89% in high-income countries; USA funds 39% of all grants > Research focus: 56% basic research/prevention; only 24% on clinical trials/treatment/health services > Funding gap: Despite 290M DALYs burden, mental health receives only 2% of domestic government healthcare funding globally > Annual funding gap: $200-350 billion needed > — Lancet Global Health: Mental Health Matters | United GMH: Financing Mental Health | ScienceDirect: Accounting for Mental Health Research Funding > Note: “$1.5B/year” understated. Actual: $3.7B/year (2015-2019 data). Still severely underfunded relative to disease burden
Global mental health research spending: ~$3 billion > Actual: $3.7 billion/year (2015-2019 data per Lancet Psychiatry 2020) > See #global-mental-health-research-spending-1-5b for full details > — Lancet Global Health: Mental Health Matters > Note: “$3B” is close to actual $3.7B/year. More accurate than earlier “$1.5B” claim
Global military spending of $2.44 trillion annually > “Global military spending: $2.44 trillion annually” > — SIPRI, 2025, Trends in World Military Expenditure, 2024 | Note: 2024 spending reached $2.718 trillion, up 9.4% from 2023 | SIPRI Military Expenditure Database, Database
Annual number of new drugs approved globally: ~50 > 50 new drugs approved annually > — C&EN, 2025, 50 new drugs received FDA approval in 2024 | FDA, Novel Drug Approvals | Note: Average ~50 per year 2018-2024; 32 small molecules + 18 biologics in 2024
Global nuclear weapon maintenance cost: $100 billion/year > 2024: >$100 billion ($190,151/minute) - 11% increase ($9.9B) from 2023 > Nine nuclear-armed states: China, France, India, Israel, N. Korea, Pakistan, Russia, UK, US > US: $56.8B (more than all other 8 states combined); China: $12.5B; UK: $10B (+26% YoY, biggest increase) > Historical trend: $72.9B (2019) → $82.4B (2021) → >$100B (2024) > Private sector contracts: $463B ongoing; $42.5B earned from contracts in 2024 alone > — ICAN: Global Spending $100B 2024 | ICAN: The Cost of Nuclear Weapons > Note: $100B/year figure accurate for 2024. Rapid growth from $73B (2019). US spends more than rest of world combined on nuclear weapons
Global population reaches 8 billion > Milestone: November 15, 2022 (UN World Population Prospects 2022) > “Day of Eight Billion” designated by UN > Added 1 billion people in just 11 years (2011-2022) > Growth rate: Slowest since 1950; fell under 1% in 2020 > Future: 15 years to reach 9B (2037); projected peak 10.4B in 2080s > Projections: 8.5B (2030), 9.7B (2050), 10.4B (2080-2100 plateau) > — UN: World Population 8 Billion Nov 15 2022 | UN: Day of 8 Billion | Wikipedia: Day of Eight Billion > Note: Milestone reached Nov 2022. Population growth slowing; will take longer to add next billion (15 years vs 11 years)
Global rare disease research spending > NIH rare disease funding: ~$6.9 billion (recent years per Statista) > NIH RDCRN grants (FY2019): $31M to 20 research teams + $7M data coordinating center > Orphan Drug Act (1983): Incentivizes rare disease drug development (<200K people in US) > Context: ~7,000-10,000 rare diseases identified; only 5% have FDA-approved drug; up to 15% have ≥1 drug in development > — Statista: Rare Diseases Funding NIH | NIH: Funding Bolsters Rare Diseases Research > Note: $6B figure accurate for NIH rare disease funding. Vast majority of 7,000-10,000 rare diseases lack treatments despite significant funding
Global rare diseases research spending: ~$2 billion > See #global-rare-disease-research-spending-6b for accurate data > NIH alone funds ~$6.9B for rare diseases > — Statista: Rare Diseases Funding NIH > Note: “$2B globally” is UNDERSTATED. NIH alone spends $6.9B on rare disease research. Global total likely higher when including other countries’ funding
Global annual spending on housing > Market value estimates vary widely: > Statista: $654.39T total market value (2025 projection) > Current market size: $4.06-4.36T (2024-2025) → $7.84T projected (2033); CAGR 7.6% > Allied Market Research: $28.9T (2021) → $48.9T projected (2031) > Residential real estate: $11.6T (2025) → $23.5T projected (2033) > Real estate loans (not total market): $7.97T (2020) → $23.1T projected (2030) > — Statista: Real Estate Worldwide | Straits Research: Real Estate Market | Grand View Research: Real Estate Market > Note: “$23T” likely refers to projected 2030-2033 residential real estate market or real estate loans, not current annual spending. Current market: $4-12T depending on methodology
Global annual spending on transportation (cars & planes) > 2023: $7.90T → 2032 projected: $15.90T; CAGR 8.10% > 2024: $8.54T → 2034 projected: $18.63T; CAGR 8.11% > Segments: Road, Rail, Air, Maritime, Pipeline, Intermodal, Courier/Parcel, E-Commerce, Specialized > Vehicle types: Cars, Trucks, Buses, Vans, Rail Cars, Ships, Aircraft > Auto sales: 75.3M cars (2023), up from 67.3M (2022) > Air traffic: +36% passenger demand (2023 vs 2022); +12% projected (2024) > — Business Research Company: Transport Market 2025 | Precedence Research: Transportation Services | Cervicorn: Transportation Market $17.23T by 2034 > Note: “$12T” overstated for current market. Actual 2024: ~$8T. Will reach $12T around 2028-2029 based on current growth trajectory
Global university student population of 20 million > 2025: 264 million students (record, +25M since 2020, >2X the 2000 total) > 2020: 235 million; 2000: 100-107 million; 2014: 207 million; 2016: 216 million > Projected: 380M (2030), 472M (2035), 594M (2040) > Gender: Women outnumber men globally (113 women per 100 men, 2023) > Regional: Sub-Saharan Africa 9% enrollment vs 43% global average > Growth: More than doubled 2000-2025 > — UNESCO: Record 264M Students 2025 | ICEF: Growth Through 2040 > Note: “20M” is DRASTICALLY understated. Actual: 264M (2025) - more than 13X higher than claimed!
Global video games market size: $85 billion > 2024 actual: $178-299 billion (varies by source), NOT $85B > Newzoo: $187.7B (2024, +2% YoY); updated: $177.9B > GamesIndustry: $184.3B (2024, +0.2% YoY) > Visual Capitalist/Newzoo: $182.7B (2024) > Grand View Research: $299B (2024) > Precedence Research: $274.63B (2024) > Mobile games: $92.5B (~50% of market, +2.8% YoY, only growing segment) > — Grand View Research: Video Game Market | Statista: Games Worldwide | Visual Capitalist: Video Game Revenue 2024 > Note: “$85B” is SIGNIFICANTLY understated. Actual 2024: $178-299B (2.1-3.5X higher than claimed)
Global Cost of Violence > “The economic impact of violence on the global economy in 2021 was $16.5 trillion, equivalent to 10.9% of global GDP, or $2,117 per person.” > — Institute for Economics & Peace, 2022, Global Peace Index
General Motors lobbying for electric vehicle subsidies > 2025: GM + Ford lobbying Trump admin/GOP to preserve IRA EV incentives; propose 3-year wind down > IRA removed 200K vehicle cap; GM/Tesla lost credit in 2018-2019, regained it post-IRA > GM contracted multiple lobbying firms: Polaris-Hutton, DS2 Group, S-3 Group > GM hired Everett Eissenstat (Trump’s fmr deputy asst for intl econ affairs) as SVP global public policy > Leasing loophole: Any vehicle gets full $7,500 regardless of battery origin/lessee income > GM pushes to apply US sourcing standards to leases (currently only purchases), disadvantaging Asian/European automakers > — TT News: GM Ford Lobby to Save EV Tax Incentives | CBS: GM Lobbying Blitz | Bloomberg: Ford GM Toyota Lobby > Note: Extensive lobbying demonstrates incentive alignment works. GM pivoted strategy to protect subsidies while advocating stricter sourcing rules against foreign competitors
Death toll of China’s Great Leap Forward (1958-62) > Great Leap Forward (1958-62) | 15-55 million (consensus: 30-45M) > Ashton et al. (1984): ~30 million premature deaths > Frank Dikötter: At least 45 million (including 2.5M tortured/summarily killed) > Yang Jisheng: 36 million (“Tombstone”, 2008) > General consensus: ~40 million deaths > Regarded as deadliest famine & one of greatest man-made disasters in history > Liu Shaoqi (1962): 70% human error, 30% natural disasters > — Wikipedia: Great Leap Forward | Wikipedia: Great Chinese Famine | History in Charts: Death Toll | SCMP: 45 Million Died
Economic value and lives saved by the Green Revolution > Norman Borlaug’s Green Revolution: Over 1 billion lives saved from starvation > Pakistan wheat: 4.6M tons (1965) → 7.3M tons (1970) - nearly doubled > India wheat: 12.3M tons (1965) → 20.1M tons (1970) - 64% increase > World grain supply: Grew 150% from 1950 to 1992 > Recognition: 1970 Nobel Peace Prize; “saved more lives than any man in human history” (Josette Sheeran, WFP, 2009) > Congressional Tribute to Dr. Norman E. Borlaug Act of 2006: “more than a billion people” > “Billion lives saved” = estimate of deaths prevented based on Gregg Easterbrook (1997) & Dennis T. Avery > — Wikipedia: Norman Borlaug | World Food Prize: About Borlaug | All That’s Interesting: Saved A Billion Lives | University of Minnesota: Saved A Billion Lives > Note: Economic value not precisely quantified in sources; billion lives saved is widely cited estimate
Terror attack deaths (8,300 annually) > 2023: 8,352 deaths (22% increase from 2022, highest since 2017) > 2023: 3,350 terrorist incidents (22% decrease), but 56% increase in avg deaths per attack > Global Terrorism Database (GTD): 200,000+ terrorist attacks recorded (2021 version) > Maintained by: National Consortium for Study of Terrorism & Responses to Terrorism (START), U. of Maryland > Geographic shift: Epicenter moved from Middle East to Central Sahel (sub-Saharan Africa) - now >50% of all deaths > — Our World in Data: Terrorism | Global Terrorism Index 2024 | START Global Terrorism Database | Our World in Data: Terrorism Deaths
The Nine Hallmarks of Aging > Nine hallmarks of aging (López-Otín et al., 2013): > 1. Genomic instability, 2. Telomere attrition, 3. Epigenetic alterations, 4. Loss of proteostasis, 5. Deregulated nutrient-sensing, 6. Mitochondrial dysfunction, 7. Cellular senescence, 8. Stem cell exhaustion, 9. Altered intercellular communication > Categories: (a) Primary hallmarks (unequivocally deleterious: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis); (b) Antagonistic hallmarks (beneficial at low levels, deleterious at high: deregulated nutrient sensing, cellular senescence, mitochondrial dysfunction); (c) Integrative hallmarks (affect tissue homeostasis: stem cell exhaustion, altered intercellular communication) > — PubMed: The Hallmarks of Aging | Cell: The Hallmarks of Aging | PMC: The Hallmarks of Aging | Cell: Telomeres & Hallmarks
Hayek’s Nobel Prize for Economic Science > Friedrich August von Hayek (1899-1992): Nobel Memorial Prize in Economics, October 9, 1974 > Shared with: Gunnar Myrdal (Swedish economist) > Citation: “for their pioneering work in the theory of money and economic fluctuations and for their penetrating analysis of the interdependence of economic, social and institutional phenomena” > Austrian-born British economist & philosopher, major contributor to Austrian school of economics > Note: Hayek was surprised by the award and believed he was paired with Myrdal (opposite political spectrum) for balance; he later said if consulted, he would have advised against establishing a Nobel Prize in economics > — Nobel Prize: 1974 Economic Sciences | Wikipedia: Friedrich Hayek | Britannica: F.A. Hayek | Econlib: Friedrich August Hayek
840,000 QALYs gained annually > This is an INTERNAL PROJECTION from this book’s economic model, NOT an external citation > Projection: 840,000 QALYs/year (base case) from dFDA implementation > Range: Conservative: 190,000 QALYs/year | Base: 840,000 | Optimistic: 3,650,000 > Components: Faster drug access (200k base), enhanced prevention via RWD (140k base), new therapies for rare/neglected diseases (500k base) > QALY definition: One year in perfect health = 1 QALY; scores range from 1 (perfect health) to 0 (dead) > Calculation: Change in utility value induced by treatment × duration of treatment effect > Used in economic evaluation to assess value of medical interventions; combines length & quality of life into single index > — Internal model: Appendix: Detailed QALY Calculation Model | QALY background: Wikipedia: Quality-adjusted life year | PMC: Calculating QALYs | Physiopedia: QALY | York Health Economics: QALY
$4.5 trillion annual healthcare cost savings (US) > “Healthcare cost savings: $4.5 trillion annually (US alone) approaching zero” > IMPORTANT: $4.5T is total US healthcare SPENDING (2022), NOT potential savings > Actual prevention savings estimates: $16B annually (from $10/person community programs), $45B/year (disease management/case management), $26B (diabetes/obesity/smoking prevention) > Current spending: $4.9T annual healthcare expenditures (90% for chronic & mental health conditions) > — CDC: Health Expenditures | Medical Economics: $4.5T in 2022 | PMC: Improving Healthcare Prognosis | NCBI: Missed Prevention Opportunities
Healthcare investment economic multiplier (1.8) > Healthcare fiscal multiplier: 4.3 (95% CI: 2.5-6.1) during pre-recession period (1995-2007) > Overall government spending multiplier: 1.61 (95% CI: 1.37-1.86) > Why healthcare has high multipliers: No effect on trade deficits (spending stays domestic); improves productivity & competitiveness; enhances long-run potential output > Gender-sensitive fiscal spending (health & care economy) produces substantial positive growth impacts > — PMC: California Universal Health Care | CEPR: Government Investment | PMC: Health Sector Investment & Growth | ODI: Fiscal Multipliers Review > Note: “1.8” appears to be conservative estimate; research shows healthcare multipliers of 4.3
60 million healthcare workers globally > 2020: 65.1 million health workers globally (29.1M nurses, 12.7M doctors, 3.7M pharmacists, 2.5M dentists, 2.2M midwives, 14.9M additional occupations) > Earlier WHO data: 59.8 million health workers (approximately 60M) > Distribution: 39.5M provide health services, 19.8M management & support > Projected 2030: 84 million health workers (29% growth from 2020) > Workforce shortage: 15M shortage in 2020, projected 10M shortage by 2030 > — PubMed: Global Health Workforce 2020-2030 | WHO: Global Health Workforce Statistics | PMC: Health Workforce Distribution | WHO Global Health Learning: Workforce Shortage > Note: 60M is accurate for earlier estimates; most recent 2020 data shows 65.1M
Helios (end-to-end verifiable voting) > “Helios is an open-audit voting system… voters can verify that their vote is included and correctly tallied.” > — Adida et al., Helios, heliosvoting.org
Historical life expectancy around 30 years > Average life expectancy at birth: ~30 years for most of human history until 1800s > 1820: Global average still ~30 years; 1800-2000: Rose from 30 to 67 years > Context: Low life expectancy driven primarily by high infant mortality (~1/3 of children died before age 5) > Medieval England: Life expectancy at birth = 31.3 years, but life expectancy at age 25 = 25.7 additional years (total 50.7) > Roman Egypt: Average in 20s, but many lived into 40s+ if they survived childhood > — Our World in Data: Life Expectancy | PMC: Changing Life Expectancy | USC: Old Age Not Modern Phenomenon | Discover: Life Expectancy Ancient Humans
Howey Test Securities Definition > “The test is whether the scheme involves an investment of money in a common enterprise with profits to come solely from the efforts of others.” > — Supreme Court, Case Link
Human Genome Project and CRISPR Discovery > Your DNA is 3 billion base pairs > Read the entire code (Human Genome Project, completed 2003) > Learned to edit it (CRISPR, discovered 2012) > — NHGRI, International Consortium Completes Human Genome Project | Nobel Prize, The Nobel Prize in Chemistry 2020 | Note: HGP cost ~$2.7B; CRISPR discovered by Doudna & Charpentier in 2012
Estimated Chemical Reactions in the Human Body > 37 thousand billion billion (37 × 10^21) chemical reactions per second > Calculation: ~1 billion (10^9) reactions/second/cell × 37 trillion (37 × 10^12) cells > Range: Some estimates suggest 3.7 × 10^22, others up to septillions (10^24) per second > Cell count: 37.2 trillion cells (most current estimate) > Variation: Each cell can host thousands of simultaneous chemical reactions; estimates per cell range from hundreds of millions to several billion > — Step One Foods: 37 Billion Billion | Biology Insights: Chemical Reactions | ECHEMI: Chemical Reactions in Body
Violence in Hunter-Gatherer Societies > “The proportion of deaths due to warfare among hunter-gatherers ranges from 15% to 30% of all deaths.” > — Pinker, Steven, 2011, The Better Angels of Our Nature
Hypertension Screening & Treatment Cost per QALY > “The estimated cost per QALY gained for screening was less than $1000 for men and approximately $1600 for women.” > — PMC5217841, Link
International Campaign to Ban Landmines (ICBL) > “The Convention was opened for signature at Ottawa, Canada, by all States from 3 December 1997 until 4 December 1997.” > — ICBL, The Treaty
ID.me digital identity verification service > Trusted technology partner to multiple US government agencies for secure digital identity verification > Scale: Serves 20 federal agencies, 44 state government agencies, 66 healthcare organizations > Use cases: Unemployment, Tax, Retirement, Centers for Medicare/Medicaid > 2013: Awarded 2-year grant by US Chamber for President’s National Strategy for Trusted Identities in Cyberspace (NSTIC) > 2014: Won contract with General Services Administration for Connect.gov digital identity credentials > COVID-19 pandemic: Contracted by several state unemployment agencies to verify claimants > Standards: NIST 800-63-3 establishes guidelines for identity verification providers serving federal agencies > Privacy concerns: IRS announced (Feb 2022) new authentication option without biometric data including facial recognition > — ID.me: Government Services | Wikipedia: ID.me | ID.me: About | ID.me: Public Sector
IEA Net Zero Roadmap cost for energy transition > 2023: Record $1.8 trillion invested in clean energy; needs to climb to ~$4.5 trillion/year by early 2030s to align with net zero > Energy investment: 2017-2021 = 2% of global GDP annually; rises to ~4% by 2030 in Net Zero Emissions (NZE) Scenario > Electricity generation from renewables: $390B recent years → $1,300B by 2030 > Public demonstration projects: $90B needed globally before 2030 > Universal energy access: $40B/year (1% of average annual energy sector investment) > — IEA: Net Zero by 2050 | IEA PDF: Net Zero Roadmap | WRI: 5 Things About IEA Roadmap
Illinois Biometric Information Privacy Act (BIPA) > Enacted: October 3, 2008 (introduced Feb 14, 2008 by State Sen. Terry Link; passed both Houses July 10, 2008; signed by Gov. Rod Blagojevich) > Purpose: Regulate collection, use, and handling of biometric identifiers and information by private entities in Illinois > Requirements: Written notice of what data is collected/stored, specific purpose & duration, obtain written consent > Covered biometrics: Retina/iris scans, fingerprints, voiceprints, hand scans, facial geometry, DNA, other unique biological info > Prohibitions: Selling or profiting from consumers’ biometric information > Penalties: $1,000 per violation; $5,000 per intentional/reckless violation > Private right of action: Any aggrieved individual can sue > 2024 update (SB2979): Multiple collections from same person = single violation (single recovery per individual) > — ACLU Illinois: BIPA | Wikipedia: BIPA | Securiti: Illinois BIPA Overview | Winston & Strawn: What Is BIPA
NIH rejection of early immunotherapy research > William Coley (1862-1936): Developed “Coley’s toxins” (1891) - bacteria/bacterial products to treat cancer (first immunotherapy) > Coley faced opposition from medical establishment, not NIH rejection (NIH didn’t exist in modern form during his time) > 1894: JAMA issued statement criticizing use of his toxins > 1962: FDA refused to acknowledge toxin as proven drug, made it illegal to treat cancer > Early funding: Small Rockefeller donations; 1902 large grant from Huntington family > Steven Rosenberg: Currently chief of surgery & head of tumor immunology at NCI/NIH (no evidence of NIH rejection) > 30+ years ago: NCI intramural scientists began exploring using immune system to fight cancer > — Cancer Research Institute: Coley’s Toxins | Wikipedia: Coley’s toxins | PMC: Talkin’ Toxins | Wikipedia: William Coley | NIH: Rosenberg Immunotherapy Pioneer
Impact investing regulatory reform > “Reforms to securities regulation can better support impact investing while maintaining investor protections.” > — Brookings, 2022, Policy to Support Impact Investing
India medical research spending: $1.2 billion > Current pharma & MedTech R&D: ~$3 billion (vs US $50-60B, China $15-20B) > Department of Health Research budget 2025-26: Rs. 3900.69 crores ($467M USD) > Recent budget: Rs 3,201 crore ($419.2M) > Historical health research funding: US $1,053M (2007-08) → $1,423M (2011-12), 8.8% annual increase > Public health spending: ~1.2% of GDP (among lowest globally) > Healthcare infrastructure need: $1.2 trillion (NITI Aayog 2022 report) > — ACS: India Budget Biotech Health | National Medical Journal of India: Health Research Funding | Dept of Health Research: Budget Reports > Note: “$1.2 billion” may refer to historical 2011-12 figure ($1.423B). Current: $3B pharma/MedTech, $467M govt budget
Indian Aadhaar national identity system > Largest biometric identity system in history: ~1 billion registered users (nearly all of India’s 1.4B population) > 12-digit unique identification number issued by Unique Identification Authority of India (UIDAI) > Biometric data: Fingerprints, facial images, iris scans stored in Central Identities Repository (national centralized database) > Privacy concerns: Deployed without direct legislative privacy/ethics constraints; comprehensive data protection legislation not yet passed > Security issues: High-ranking official’s Aadhaar number shared on Twitter led to hackers accessing personal info (mobile, tax ID) > 2017: Supreme Court enshrined privacy rights > Supreme Court ruling: 4 of 5 judges allowed program to continue with limited scope & restrictions on data storage > Threats: Potential for 360-degree profiling; viewed by many as mass surveillance tool infringing privacy rights > — PMC: Aadhaar Failure to Do No Harm | TIME: India Supreme Court Upholds | Privacy International: Aadhaar Analysis | Yale Insights: Billion Identities Digitized > Note: “with privacy protections” is questionable - significant privacy concerns remain despite Supreme Court restrictions
Infrastructure investment economic multiplier (1.6) > Infrastructure fiscal multiplier: ~1.6 during contractionary phase of economic cycle > Average across all economic states: ~1.5 (meaning $1 of public investment → $1.50 of economic activity) > Time horizon: 0.8 within 1 year, ~1.5 within 2-5 years > Range of estimates: 1.5-2.0 (following 2008 financial crisis & American Recovery Act) > Italian public construction: 1.5-1.9 multiplier > US ARRA: 0.4-2.2 range (differential impacts by program type) > Economic Policy Institute: Uses 1.6 for infrastructure spending (middle range of estimates) > Note: Public investment less likely to crowd out private activity during recessions; particularly effective when monetary policy loose with near-zero rates > — World Bank: Infrastructure Investment as Stimulus | Global Infrastructure Hub: Fiscal Multiplier | CEPR: Government Investment | Richmond Fed: Infrastructure Spending
History of insulin patent and modern price disparities > 1923: Frederick Banting, Charles Best, James Collip sold insulin patent to U. of Toronto for $1 each (total $3) > Banting: Unethical for doctor to profit from life-saving discovery; wanted everyone to afford it > Manufacturing cost: $6 per vial > US retail price: ~$300-332 per vial (Humalog: $21 in 1999 → $332 in 2019 = 1,000%+ increase) > Price increases: 600% over 20 years; 200% between 2007-2018 > Patients without insurance: Up to $1,000/month > Contributing factors: Patent evergreening, barriers to biosimilar entry, market concentration (Eli Lilly, Novo Nordisk, Sanofi) > — Snopes: Insulin Patent Dollar | T1International: 100 Years Gift to Greed | PNHP: Why Insulin is Overpriced | NPR: Skyrocketing Price of Insulin
Intelligence spending as percentage of military budgets > US: Military-related budget lines (DoE, State Dept, National Intelligence Program) = 11% of US spending (2024) > Intelligence funding: Grew faster than defense when defense spending increased; decreased slower when defense spending decreased > Historical trend: Intelligence funding reached level 80% above 1980 baseline > US National Intelligence Program + Military Intelligence Program ≈ 10-11% of total defense-related spending > — US Government Info: Cost of Intelligence | FAS: Intelligence Community Spending Trends | Wikipedia: US Intelligence Budget
Estimated deaths due to FDA delay in approving Interleukin-2 > 1985: Initial efficacy demonstrated (3 of 3 metastatic renal cancer patients showed tumor regression) > 1992: FDA approved for metastatic renal cell carcinoma (7-year gap from initial demonstration) > 1998: FDA approved for metastatic melanoma > First drug approved specifically for kidney cancer (affecting ~10,000 people annually) > Early trials: Single arm, uncontrolled; 2-4% therapy-related deaths in melanoma and RCC > — C&EN: IL-2 FDA Market Clearance | PMC: IL-2 for Renal Cancer | PMC: Contemporary IL-2 Experience > Note: “Thousands died waiting” not specifically quantified in sources; 7-year gap between efficacy demonstration (1985) and approval (1992) for disease affecting 10,000 annually
Economic value created by the internet from DARPA investment > DARPA’s initial investment: $1M contract to BBN (Jan 1969) for ARPANET; DARPA spends ~$3.5B/year total (<1% of US public/private R&D) > First signal: UCLA to Stanford Research Institute (Oct 29, 1969) > Economic value estimates: Consumer surplus ~$8T/year in $20.5T US economy; IoT projected $11.1T/year by 2025 > Internet’s trillion-dollar impact on global economy via Mosaic browser revolution in communications, business, education, entertainment > — NBER: Pre-commercial Internet under DARPA | DARPA: ARPANET Vignette | DARPA: ARPANET Timeline | NSF: Birth of Commercial Internet > Note: “$10T+ annual value” is reasonable estimate; consumer surplus alone ~$8T/year, IoT projections $11.1T/year by 2025
Over 50 million people in the investment community > Vanguard: “community of 50 million” refers to their investor client base, not investment professionals > CFA Institute: 175,000+ CFA® charterholders worldwide in 160+ markets (professional investment community) > Investment Company Institute (ICI): Members manage $32.3T US assets serving 100M+ US shareholders, $9.6T in other jurisdictions > — CFA Institute: About | Wikipedia: Investment Company Institute > Note: “50M investment community” appears to conflate investor clients with investment professionals. Actual professional community substantially smaller (e.g., 175K CFA charterholders)
Investment Return Comparison > “Over the past five years, the average annual return for major defense contractors has been approximately 8%, while leading healthcare companies have yielded average annual returns of around 12%.” > — Forbes, 2024, Healthcare Stocks Poised for a Rebound
Journal of the American Medical Association (JAMA) founded in 1883 > Founded: 1883 by American Medical Association > Founding editor: Nathan Smith Davis > Superseded: Transactions of the American Medical Association > 1960: Obtained current title “JAMA: The Journal of the American Medical Association” > Evolution: Late 1800s resembled general journalism; 1910s-1920s “turndown era” began rejecting submissions based on quality; routine peer review instituted after WWII > Current: Peer-reviewed medical journal published 48 times/year covering all aspects of biomedicine > — Wikipedia: JAMA | JAMA Network: History of AMA | Penn: JAMA Archives
James Buchanan Nobel Prize in Economics, 1986 > James McGill Buchanan: 1986 Nobel Memorial Prize in Economic Sciences > Citation: “for his development of the contractual and constitutional bases for the theory of economic and political decision-making” > Field: Public choice theory (leading researcher & cofounder with Gordon Tullock) > Key work: “The Calculus of Consent” (with Tullock) - now considered a classic, started the field > Contribution: Transferred concept of gain from mutual exchange between individuals to political decision-making; applied economic analysis to public sector > Inspiration: Swedish economist Knut Wicksell (described as “most exciting intellectual moment” of career) > — Nobel Prize: 1986 Economic Sciences | Wikipedia: James M. Buchanan | Britannica: James M. Buchanan | Econlib: James M. Buchanan
Japan medical research spending: ~$5 billion/year > Publicly competitive health R&D funding: 344.1B JPY (~$3B USD) for 32,204 projects in 2015-2016 > Japan Agency for Medical Research & Development (AMED): ~660B yen (~$6B USD) funded since establishment > Pharmaceutical R&D: 1.43 trillion yen (~$13B USD) by Japanese pharma companies in FY2022 > Total R&D across all fields (FY2022): 20.7 trillion yen (most for natural sciences including health) > — PMC: Limited Alignment Disease Funding Japan | Nature: Promoting Better Medical Research Japan | PMC: Effectiveness Japanese Public Funding | Statista: Japan Pharma R&D > Note: “$5B” is reasonable estimate for government health R&D; AMED alone ~$6B total; pharma private R&D much higher (~$13B)
Japan’s Regenerative Medicine Act and conditional approval pathway > Act on Safety of Regenerative Medicine (RM Act) + amended Pharmaceuticals and Medical Devices Act (PMD Act): passed Nov 2013, effective Nov 2014 > Conditional and time-limited approval pathway: Obtain approval after exploratory trials demonstrate probable benefit and proven safety > 7-year conditional approval period to confirm clinical benefit (e.g., using surrogate endpoints) > SAKIGAKE designation (April 2015): Expedited pathway for innovative products targeting serious/life-threatening diseases without effective treatment > Benefits: Prioritized consultation, accelerated review, extended re-examination period, premium pricing > Examples: Terumo’s HeartSheet and Stemirac obtained conditional approval; Stemirac also SAKIGAKE-designated > — FDLI: Japan’s Regen Med Pathways | Cell & Gene Therapy Insights: SAKIGAKE | PMC: Flexible Regulatory Review Japan
Johnson & Johnson 2023 Financials > “Johnson & Johnson reported revenues of $85.2 billion and a net income of $35.2 billion in 2023, resulting in a profit margin of about 41%.” > — Johnson & Johnson, 2024, Investor Relations
Death toll of the Khmer Rouge regime (1975-79) > Cambodian genocide (1975-79): 1.5-2 million deaths (nearly 25% of Cambodia’s ~7.8M population in 1975) > Most widely accepted estimates: 1.5-2M excess deaths (range: 1M-3M depending on source) > Verified execution victims: At least 1,386,734 (from analysis of 20,000 grave sites) > Different estimates: 1.7-2.2M from disease/starvation/execution combined > — Wikipedia: Cambodian Genocide | Britannica: Khmer Rouge | UCLA: Cambodia Death Toll Estimate | USHMM: Cambodia 1975-1979
Annual deaths from kidney disease > Direct CKD deaths: 1.2M (2017), 1.53M (2021); increased from 591,800 (1990) to 1,425,670 (2019) > CKD-attributable cardiovascular deaths: Additional 1.4M deaths from CVD attributable to impaired kidney function (7.6% of all CVD deaths, 2017) > Combined impact: 4.6% of total global mortality > CKD: 12th leading cause of death globally; one of few NCDs showing increased deaths over past 2 decades > — National Kidney Foundation: Global Facts | PMC: Epidemiology CKD 2022 | Lancet: Global Burden CKD 2017 | IHME: CKD Global Killer
Approval of Landmark Gene Therapies (Luxturna, Zolgensma, CAR-T) > Luxturna (Dec 2017): First in vivo gene therapy approved by US FDA; treats biallelic RPE65 mutation-associated retinal dystrophy (inherited blindness); $850,000 one-time therapy > CAR-T therapies (2017): Kymriah and Yescarta approved same year as Luxturna > Zolgensma (May 2019): Spinal muscular atrophy treatment; second gene therapy for inherited disease in US; $2.1M (one of most expensive medicines at the time) > Described as “landmark moment for a field riddled with ups and downs” and “landmark achievements in history of modern science” > — BioPharma Dive: Luxturna | C&EN: First Gene Therapy Genetic Disease | NPR: First Gene Therapy Inherited Disease | PMC: Recombinant AAV Gene Therapy
Landray, Sir Martin, on the RECOVERY Trial > “In 2019, I had no idea that I would be setting up a trial of treatments for an infectious disease, let alone a pandemic virus. > I certainly would not have thought it possible to go from a blank piece of paper to enrolling the first patient in nine days, to finding the first life-saving treatment within ten weeks, and for it to be made standard NHS policy within three hours.” > — Sir Martin Landray, Oxford University News
Price drops in cash-based medical markets > LASIK early 2000s price decline: ~20% drop to $1,600/eye (2000-2002), not 50% > Free market dynamics: Not covered by insurance/Medicaid/Medicare; sold in free market with price advertising & competition > Increased competition from more trained physicians led to falling prices > Current pricing (2024): Average $2,246/eye; range $1,500-3,000/eye (relatively stable past 2 decades) > Cash-pay nature: Most patients pay out of pocket for elective/cosmetic procedure > — Healthcare Economist: LASIK Markets at Work | All About Vision: LASIK Cost 2024 | CRSToday: Retail Pricing Refractive Surgery
Leading causes of death by age group > Teenagers (12-19): Accidents (nearly half), homicide, suicide, cancer, heart disease; motor vehicles represent >1/3 of all deaths > Young adults (15-24): Unintentional injuries (mainly auto accidents & substance use, ~half); suicide (19.6%); homicide > Ages 10-34: Accidents leading cause; homicide & suicide second/third (common for young age groups) > Ages 25-44: Unintentional injuries (mainly opioid overdoses & car accidents); suicide, homicide, heart disease; cancer & liver disease gain prominence > Pattern: For all groups under 40, unintentional injuries (accidents) are leading cause, followed by suicide & homicide > — NCBI: Leading Causes by Age | CDC NVSS: Leading Causes | USAFacts: Causes Death by Age | CDC WISQARS: Leading Causes by Age 2021
Contribution of smoking reduction to life expectancy gains > Population-level: Up to 14% (9% men, 14% women) of total life expectancy gain since 1960 due to tobacco control efforts > Individual cessation benefits: Quitting at age 35 adds 6.9-8.5 years (men), 6.1-7.7 years (women) vs continuing smokers > By cessation age: Age 25-34 = 10 years gained; age 35-44 = 9 years; age 45-54 = 6 years; age 65 = 2.0 years (men), 3.7 years (women) > Cessation before age 40: Reduces death risk by ~90% > Long-term cessation: 10+ years yields survival comparable to never smokers, averts ~10 years of life lost > Recent cessation: <3 years averts ~5 years of life lost > — PMC: Benefits Smoking Cessation Longevity | CDC: Estimating Benefits Smoking Reductions | AJPM: Benefits Quitting Different Ages | NEJM: 21st-Century Hazards & Benefits
Claim of linear 4-year life expectancy increase from 1890-1960 > Global life expectancy increased from 32 years (1900) to 73 years (2023) - more than doubled > This represents an average increase of 41 years over 123 years > — Our World in Data: Life Expectancy | WHO: Global Health Estimates
Defense industry lobbying spending > “During the first three quarters of 2022, the defense sector spent approximately $101 million on lobbying activities.” > “Military industry lobbying totaled over $100 million in 2024.” > — Watson Institute, Brown University, 2022, Defense Sector Lobbying | OpenSecrets, 2024, Defense industry lobbying totals
Lobbying impact on NIH funding > “Lobbying for specific diseases, such as AIDS and breast cancer, is associated with a disproportionate increase in NIH funding compared to the burden of the disease.” > — BMJ via PMC, 1999, Role of advocacy in allocation of NIH funds
Lobbying ROI Calculation ($1,813 per $1) > “The top five defense firms received $2.02 trillion in contracts from the Pentagon during the 20 years of the war in Afghanistan… > Over the past two decades, the top five defense contractors have spent $1.1 billion on lobbying… > That calculates to an ROI of $1,813 for every dollar spent.” > — Responsible Statecraft, 2021, Top 5 Defense Firms See $2T Return on $1B Investment in Afghan War
Lobbying ROI Feasibility > “Policy-influenced investments can yield high ROIs when backed by public mandates.” > — Watson Institute, Brown University, 2022, Profits of War
Lobbying ROI for NIH funding > “Each $1,000 spent on lobbying is associated with an average of $25,000 in extra NIH funding, indicating non-scientific allocation of capital.” > — Nature, 2014, Lobbying for research funding reaps rewards
Lobbying Spend (Defense) > “Military industry lobbying totaled ~$127 million in 2024.” > — OpenSecrets, 2024, Defense Lobbying
Lobbyist statistics for Washington D.C. > Registered lobbyists: Over 12,000 (some estimates); 12,281 registered (2013) > Former government employees as lobbyists: 2,200+ former federal employees (1998-2004), including 273 former White House staffers, ~250 former Congress members & agency heads > Congressional revolving door: 43% (86 of 198) lawmakers who left 1998-2004 became lobbyists; currently 59% leaving to private sector work for lobbying/consulting firms/trade groups > Executive branch: 8% were registered lobbyists at some point before/after government service > — OpenSecrets: Lobbying in US | OpenSecrets: Revolving Door | Citizen.org: Revolving Congress | ProPublica: 281 Lobbyists Trump Admin
Lockheed Martin 2023 Revenue > “In 2023, Lockheed Martin earned $68.5 billion from government contracts, accounting for 9.19% of total federal contract dollars.” > — Wikipedia, 2024, Top 100 Contractors of the U.S. federal government
Lockheed Martin’s diversification into health IT > July 2015: Launched Healthcare Technology Alliance (founding: Cisco, Cloudera, Illumina, Intel, Montgomery College) > Focus: Securing patient info, genomic research, big data for public health; marketed to providers, payers, pharma, government > Nearly 2 decades healthcare IT experience: CDC, CMS, Federal Occupational Health, SSA, DoD, VA > Health team: 2,500+ clinical, scientific, technical professionals (health IT, research, bioinformatics, medical services) > Diversification driver: Sluggish defense spending led to expansion into climate, space, nuclear fusion, healthcare > — Lockheed Martin: Healthcare Alliance Launch | PR Newswire: Healthcare Alliance | Healthcare Dive: Big New Alliance | Washington Post: Tackles Health Care
Lockheed Martin’s political donations, contracts, and state operations in 2022 > Political contributions 2022: $3,946,639 (PAC + individuals); PAC alone: $1,542,500 to federal candidates (2021-2022 cycle) > Lobbying 2022: $13.6M expenditure (focused on defense appropriations, foreign military sales) > Geographic footprint: Operations in over half of states; employs 1,000-20,000+ per state > — OpenSecrets: Lockheed Martin Summary | OpenSecrets: Lockheed PAC 2022 | Taxpayer.net: Military Industry Political Footprint
The Collapse of Long-Term Capital Management (LTCM) in 1998 > Founded 1994 by John Meriwether (former Salomon Brothers vice-chairman) > Board included Nobel Prize winners: Myron Scholes & Robert C. Merton (1997 Nobel in Economics for Black-Scholes model) > Initial success: 21% (year 1), 43% (year 2), 41% (year 3) annualized returns after fees > 1998 collapse: Lost $4.6B in <4 months due to high leverage + 1997 Asian crisis + 1998 Russian crisis > Extreme leverage: $30 debt per $1 capital (end of 1997) > Bailout: $3.6B ($3.625B) from 14 banks, brokered by Federal Reserve Bank of NY (Fed didn’t lend own funds) > By early 2000: Fund liquidated, creditors repaid > — Wikipedia: LTCM | Federal Reserve History: LTCM Near Failure | Wall Street Mojo: LTCM Collapse | CFA Institute: How Financial World Almost Ended
Lost human capital due to war ($270B annually) > Lost human capital from war: $300B annually (economic impact of losing skilled/productive individuals to conflict) > Broader conflict/violence cost: $14T/year globally > 1.4M violent deaths/year; conflict holds back economic development, causes instability, widens inequality, erodes human capital > 2002: 48.4M DALYs lost from 1.6M violence deaths = $151B economic value (2000 USD) > Economic toll includes: commodity prices, inflation, supply chain disruption, declining output, lost human capital > — Think by Numbers: War Costs $74,259/Lifetime | WEF: War Violence Costs $5/Day | PubMed: Economic Value DALYs Violence
MakerDAO scale > “MakerDAO manages over $5.5 billion in assets through decentralized governance.” > — MakerDAO, 2024, Official Site.
Annual deaths from malaria > 600,000 people per year die from malaria (a disease spread by a bug we can’t figure out how to properly swat) > — WHO, 2024, World Malaria Report 2024 | Note: 597,000 deaths in 2023; 73.7% were children under 5
Manhattan Project cost in modern dollars > Original cost: $1.89 billion (1945 dollars) > Inflation-adjusted: $29.6-32.9 billion (2023-2024 dollars) > Almost two-thirds of budget spent on Oak Ridge uranium enrichment facilities > — Brookings: Costs of the Manhattan Project | MoneyZine: Manhattan Project Cost > Note: Los Alamos received just 4% of total budget. For comparison, the B-29 bomber program was more expensive than the Manhattan Project
Pharmaceutical spending on me-too drugs: $40 billion/year > $40B+ figure relates to expanded marketing budgets (continuing medical education, physician support, postmarketing research for sales expansion) > 2005: Top 4 “me-too” drug classes (statins, PPIs, SSRIs, ACE inhibitors) = $44B revenue (17% of total US sales) > Definition: Copycat drugs using basic chemical structure of existing drug with slight modifications; similar actions/structures as pioneer drugs > Debate: Critics say little incremental clinical value + higher costs; defenders note some uncover new mechanisms/effects > — Stanford Medicine: Me-too Drugs | Wikipedia: Me-too Drug | PMC: Me-Too Innovation Pharmaceutical Markets | PMC: Me-too Products History
Medical research funding trends as a percentage of GDP > NIH funding as % of GDP: Peaked 2003, declined through 2015; 2019 still 12% below 2003 levels > Historical: 0.127% GDP (1990) → 0.208% GDP (2003 peak, after doubling effort) → declined through 2015 > Federal basic research as % of R&D: 39% all-time high (2003) due to NIH budget doubling (late 1990s-early 2000s) > Inflation distortion: Biomedical research costs increased 14X (1950-2010) vs 7.5X overall inflation > Recent decline driven almost entirely by reduced private sector investment, not just NIH cuts > — American Progress: NIH Funding Erosion | ITIF: Healthy Funding | US News: US Medical Research Spending Drops
Medical research lives saved annually (4.2 million) > Physical activity: 3.9M early deaths averted annually worldwide (15% lower premature deaths than without) > COVID vaccines (2020-2024): 2.533M deaths averted, 14.8M life-years preserved; first year alone: 14.4M deaths prevented > Cardiovascular prevention: 3 interventions could delay 94.3M deaths over 25 years (antihypertensives alone: 39.4M) > Pandemic research response: Millions of deaths averted through rapid vaccine/drug development > — ScienceDaily: Physical Activity Prevents 4M Deaths | PMC: Lives Saved by COVID Vaccines | Circulation: Three Interventions Save 94M Lives | PMC: Saving Millions Pandemic Research
Medicare Clinical Trial Coverage Provisions (Social Security Act Amendments) > Medicare established under Title XVIII Social Security Act (“Health Insurance for the Aged and Disabled”) > June 7, 2000: President directed HHS to “explicitly authorize payment for routine patient care costs & complications” in clinical trials > Sept 19, 2000: CMS issued formal National Coverage Decision (NCD) > Coverage denial authority: §1862(a)(1)(E) of the Act; beneficiary protections: §1879, §1842(l), §1834(j)(4) > Routine costs defined: (1) Typically provided absent trial; (2) Required solely for investigational item/service; (3) Needed for reasonable care arising from investigational item/service > Qualifying trial requirements: (1) Evaluates item within Medicare benefit category; (2) Has therapeutic intent; (3) Enrolls patients with diagnosed disease > Exclusions: Investigational items/services, data collection/analysis services > — NCBI: Paying for Patient Care Clinical Trials | CMS: Medicare Coverage Clinical Trials NCD | NCBI: Recommendations Medicare Clinical Trial Reimbursement
Medicare and Medicaid reimbursement for clinical trial costs > Medicare (June 2000): President Clinton directed explicit authorization for routine patient care costs in clinical trials > Medicare NCD (Sept 2000): Reimburses routine care in trials same as routine care outside trials (physicians, providers, lab, diagnostics, other routine services) > Routine costs: (1) Conventional care typically provided absent trial; (2) Monitoring/prevention of complications; (3) Reasonable/necessary care arising from investigational item > Medicaid: South Carolina amended State Plan (effective Jan 1, 2022) to cover routine patient costs for members in qualifying trials per SMD# 21-005 & Consolidated Appropriations Act 2021 > Coverage extent: Items/services covered to extent they’d be covered outside trial under Medicaid State Plan or waiver > — CMS: Medicare Clinical Trial Policies | SCDHHS: Medicaid Coverage Clinical Trials | NCBI: Paying for Patient Care
Pharmaceutical lobby influence on Medicare Modernization Act of 2003 > Medicare Prescription Drug, Improvement, and Modernization Act (P.L. 108-173): Signed Dec 8, 2003 by President Bush; created voluntary Part D prescription drug benefit > “Noninterference provision”: Prohibits HHS Secretary from negotiating drug prices or establishing preferred drug list > Instead: Drug prices negotiated between manufacturers & insurance companies administering Part D plans > Pharma industry role in writing: “Noninterference clause” written with major industry involvement; drug manufacturers had major role writing & getting it through Congress > Industry lobbying: $231M spent on lobbying in 2003 (more than any other industry since 1998) > Rep. Billy Tauzin example: 2004 appointed PhRMA chief lobbyist ($2M/year rumored); responsible for including price negotiation prohibition > 2022 change: Inflation Reduction Act removed ban; Medicare can negotiate starting 2026 > — Wikipedia: Medicare Modernization Act | Health Affairs: Politics Medicare Drug-Price Negotiation | CRS: Medicare Drug Price Negotiation
Mental health global burden > “One in four people in the world will be affected by mental or neurological disorders at some point in their lives, representing [approximately] 30% of the global burden of disease.” > — World Health Organization, 2022, Mental Health Fact Sheet
Total annual grant funding for mental health nonprofits > 200+ mental health funding opportunities with $852M in resources (Instrumentl database) > Only 1.3% of all foundation funding goes to mental health (lags far behind other health issues) > Grant ranges: $500 minimum to $400M maximum; median $50,000; average $5.36M > Government (SAMHSA, NIMH): Billions of dollars in grants for mental health annually > Funding gap: 24% increase past 5 years, but still $200B gap needed for all mental health care needs > — Instrumentl: Mental Health Grants | Inside Philanthropy: Mental Health Grants | SAMHSA: Grants | Bloomerang: Mental Health Funding Resources
Meta R&D spending: $38 billion > Meta/Facebook R&D spending: $43.9 billion (2024), $38.5 billion (2023) > 14.01% increase from 2023 to 2024 > R&D intensity of 29.7% - highest among “Magnificent 7” tech companies > — MacroTrends: Meta R&D | Statista: R&D Costs of Online Companies > Note: Investment focused on AI and metaverse through Reality Labs; $46B spent on metaverse since 2021
Military Lobbying Returns > “For every dollar spent on lobbying, defense contractors receive over $100 in contracts.” > — Watson Institute, Brown University, 2022, Profits of War
Military spending economic multiplier (0.6) > Ramey (2011): ~0.6 short-run multiplier > Barro (1981): 0.6 multiplier for WWII spending (war spending crowded out ~40¢ private economic activity per federal dollar) > Barro & Redlick (2011): 0.4 within current year, 0.6 over two years; increased govt spending reduces private-sector GDP portions > General finding: $1 increase in deficit-financed federal defense spending = less than $1 increase in GDP > Variation by context: Central/Eastern European NATO: 0.6 on impact, 1.5-1.6 in years 2-3, gradual fall to zero > Ramey & Zubairy (2018): Cumulative 1% GDP increase in military expenditure raises GDP by ~0.7% > — Mercatus: Defense Spending and Economy | CEPR: WWII Spending Multipliers | RAND: Defense Spending Economic Growth
Michael Milken and the Development of the High-Yield Bond Market > Michael Milken (“Junk Bond King”): Pioneered high-yield “junk bond” market with Drexel Burnham Lambert (1970s-1980s) > Original-issue high-yield debt innovation provided hostile bidders & LBO firms enormous capital for multi-billion-dollar deals > Mid-1980s: Milken’s high-yield bond buyer network enabled rapid large-scale fundraising, facilitated LBOs (e.g., KKR) > Market growth: End of 1980s = $150B junk-bond market; Drexel became leading US financial firm with ~50% market share > Milken compensation: >$1B over 4 years (late 1980s) - US income record at the time > 1989: Indicted for racketeering/securities fraud; plea bargain to securities/reporting violations (not racketeering/insider trading) > 1990: Drexel bankruptcy & liquidation > — Wikipedia: Michael Milken | HBS: Junk Bond King Case | Britannica: Michael Milken | SEC Historical: Milken Scandal
Role of industry vs. NIH in mRNA vaccine development > mRNA vaccines: Developed by companies, not NIH > — NIAID, Decades in the Making: mRNA COVID-19 Vaccines | Johns Hopkins, The Long History of mRNA Vaccines | Note: 50+ years of public/private research; COVID vaccines developed in <12 months vs. typical 10-15 years
NASA’s annual budget > Fund NASA’s budget 680 times over > — NASA, FY 2024 Budget | The Planetary Society, NASA’s FY 2024 Budget | Note: $24.875B in FY2024 (0.37% of federal budget)
NATO O&M ratios for global spending > Operations & Maintenance (O&M): 38-50% of military spending > US FY2024: O&M cost $332B (38% of military spending), up from 28% in 1974 > 2005-2015 trend: O&M represented 40-50% of DoD total budget > NATO 2024: $1.47T total spending across 32 member countries; US $967B (66%), European members $454B (30%) > NATO equipment investment guideline: At least 20% of defense expenditures for major equipment/R&D > — USAFacts: US Military Spending | CBO: DoD O&M Trends | NATO: Defense Expenditure 2024
Net Neutrality Comments (nearly 4M, 2014-2015) > “The nearly 4 million comments submitted to the Federal Communications Commission about its proposed net neutrality rules shattered the agency’s previous record…” > — Pew Research Center, 2014, FCC’s net neutrality comment period ends with a bang
Closed-loop neuromodulation and accelerated TMS for treatment-resistant depression > Stanford SAINT/SNT (accelerated TMS): 79-90% response rates, 57-86% remission rates > Open-label study (2020): 90.48% response rate, 86.4% remission (19 of 22 participants) > RCT (2021): 71.4% response, 57.1% remission vs 13.3% and 0% for sham > UCSF closed-loop deep brain stimulation: Successful n=1 case study, rapid sustained improvement > — Stanford SAINT Study (2020) | Stanford SNT RCT (2021) | UCSF Closed-Loop Nature Medicine (2021) | Stanford News
National Institute on Aging Budget: $4.41 billion > FY2023: $4.41 billion > FY2024: $4.51 billion (+$90M for Alzheimer’s/dementia research, +$12.5M for palliative care) > FY2025 (proposed): $4.6 billion (+$137.5M from FY24) > — NIA: FY2024 Budget | NIA: FY2025 Budget
NIH administrator to scientist employment ratio > Claim: Two administrators for every one scientist > Staff composition: NIH employs “Staff Scientists” (doctoral-level researchers), “Scientist Administrators” (dual research/admin roles), plus administrative support staff > Specific ratio not verified in official NIH workforce reports > — NIH OIR: Staff Scientist | NIH: Scientist Administrators
NIH administrative costs percentage (31%) > Indirect costs (facilities & administration): Historically averaged 27-28% of total grant costs > FY2023: ~$9B indirect costs out of $35B total competitive grants (26% of total) > Institution-specific rates varied: Harvard 69%, Yale 67%, UPenn 62.5%, MIT 59%, Stanford 55% > Average base rate: ~52% overhead on direct costs (meaning $52K overhead per $100K research grant = 34% of total) > February 2025: NIH imposed 15% cap on indirect cost rates for all grants > — American Action Forum: NIH 15% Cap | Feldesman: NIH Indirect Costs
NIH All of Us Research Program outcomes and spending > Total authorized funding: ~$2.16B (not $4B) - $1.02B allocated since 2015, $1.14B authorized through 2026 via 21st Century Cures Act > Budget cut 71% over 2 years: $500M+ (2023) → $150M (2025) > Enrolled: 860,000 participants from all 50 states; 633,000+ participants with data available for research > Clinical trials completed: Zero (program is observational cohort study, not a clinical trial program) > Purpose: Collect prospective data to inform future clinical trials, provide recruitment infrastructure > — All of Us: Program Overview | NEJM: All of Us Research Program | GenomeWeb: All of Us Plans
NIH All of Us Research Program > Launched: 2015 by NIH Precision Medicine Initiative > Goal: Build diverse database of 1M+ participants to accelerate precision medicine research > Data collected: Electronic health records, genomic data, surveys, physical measurements, biosamples > Enrollment: 860,000 participants; 633,000+ with research-ready data; 487,000+ electronic health records > Fueling thousands of studies on health, disease, and equitable care approaches > — All of Us: Official Site | Wikipedia: All of Us
Annual number of papers published from NIH-funded research > Global scientific output: 2.5-2.6 million research papers published annually (all sources, not just NIH) > Worldwide S&E publication growth: 1.8M (2008) → 2.6M articles (2018), averaging ~4% annual growth > NIH-specific output example (2000): 4,451 R01 grants ($1.3B) produced 55,000 publications, 3.7M citations > Total active journals: 46,736 peer-reviewed journals (2020) publishing 3M+ articles annually > — NSF: Publications Output | Our World in Data: Scientific Publications | PMC: NIH Funding Productivity
NIH budget allocation for basic vs. clinical research > Basic research: ~54% of NIH research budget ($97B in FY2017-2021) > Clinical trials: ~22% of budget ($28B in FY2017-2021) > For drug development: Clinical trials represent only 3.3% of total NIH funding ($8.1B of $247.3B from 2010-2019) > Applied to FY2025 budget ($47.7B): ~$1.6B for drug development trials, $46.1B for everything else > NIH covers ~25% of Phase 1, ~22% of Phase 2, but only ~4% of Phase 3 trial costs > — PMC: NIH Clinical Development Spending | HHS Budget Brief > Note: NIH focuses primarily on basic research and early-phase trials; industry funds most late-stage clinical trials. NIH clinical trial spending is ~10% of industry spending for approved drugs
NIH Budget (FY 2025) > “The budget total of $47.7 billion also includes $1.412 billion derived from PHS Evaluation financing…” > — NIH, 2024, Budget Overview | NIH, Office of Budget | Note: FY2024 budget was $47.1B
NIH Common Fund overview > “The Common Fund supports cross‑cutting programs that are expected to have exceptionally high impact.” > — NIH, Common Fund Overview
NIH centralized decision-making structure > NIH structure: 27 Institutes and Centers, each with own research agenda > Office of the Director: Sets policy, plans/manages/coordinates all NIH components > Location: 9000 Rockville Pike, Bethesda, Maryland > Total NIH employees: ~20,000 > Leadership structure: Director + 27 Institute/Center directors + division chiefs + council members > Specific count of “key decision-makers” varies by definition; centralized funding decisions flow through Office of Director and IC leadership > — NIH: Who We Are | NIH: Organizational Structure
Number of diseases eradicated by the NIH > Diseases eradicated globally: Only 2 (smallpox in 1979 via $300M WHO effort over <10 years; rinderpest) > NIH role: Contributor to research/vaccine development but not sole eradicator > Near-eradication: Polio (close to achievement); measles, rubella targeted for eradication > Major achievements via vaccination: Smallpox eradicated, polio nearly eliminated, diphtheria/tetanus/measles greatly reduced > Impact: Vaccination eliminated disease in populations with high implementation rates; past 2 centuries saw enormous infectious disease control via sanitation, vaccines, antibiotics, nutrition > — PMC: Six Challenges in Eradication | PMC: Contribution of Vaccination | NCBI: Major Efforts for Disease Eradication
NIH grant system favors experienced writers > “The grant system favors experienced grant writers with extensive preliminary data, potentially costing great ideas from innovative newcomers.” > — The New York Times, 2018, Why the Medical Research Grant System Could Be Costing Us Great Ideas
NIH funding bias towards established researchers > “Critics argue that NIH’s funding policies disproportionately favor established researchers and large laboratories, potentially stifling innovation from early-career scientists. > In 2017, NIH proposed capping the number of grants per investigator to address this imbalance but retracted the plan after significant opposition.” > — Science, 2017, NIH grant cap plan is dead
NIH funding cuts and brain drain > “Following a proposed 29% cut to NIH funding in 2025, 75% of scientists are considering leaving the U.S. due to funding instability.” > — Silicon Valley Business Journal, 2025, NIH funding cuts could create a science ‘brain drain’
Comparison of NIH funding and death rates for breast cancer vs. heart disease > Breast cancer: $542M average annual funding; 42,000 deaths/year; funding-to-lethality score 179.65 > Lung cancer: $293M funding; higher mortality than breast cancer > COPD: $97M funding (7X less than breast cancer); 292,000 deaths/year (6X more deaths than breast cancer) > Heart disease: Part of cardiovascular disease burden (700,000 deaths/year for heart disease alone) > Combined impact: Cardiovascular disease, cancer, diabetes = 2/3 of all US deaths, $700B economic costs/year > Funding equity: Public research money not distributed proportionally to disease prevalence/burden; >100-fold difference in funding-to-lethality scores across cancers > — PMC: Allocation of Research Funding | PMC: Cancer Burden vs Research Spending | PubMed: Preventing Cancer, CVD, Diabetes
NIH funding follows “hot topics” > “Strong lobbies for ‘hot’ diseases like breast cancer and diabetes receive disproportionate funds, while less popular diseases like stomach cancer are underfunded.” > — PMC, 1999, Role of advocacy in allocation of NIH funds
Correlation between NIH funding priorities and disease burden > Very weak correlations: R² < 0.03 between NIH funding and 5 disease burden measures for 27 diseases > Historical (1996): r=0.62 correlation with DALYs, but explained only 39% of variance > Recent (2008-2019): Simple correlation 0.08 between disease burden increases and funding increases > 2019 analysis: Only 29% of variance in NIH funding explained by disease burden > Strongest predictor of 2019 funding: 2008 funding levels (r=0.88), revealing long-standing inefficiencies > — ScienceDirect: Persistence of Very Low Correlations | NEJM: NIH Funding vs Burden of Disease | PMC: NIH Disease Funding Levels
NIH grant success rate (~19%) > “The overall success rate for NIH research project grants was 19.1% in fiscal year 2024.” > — NIH Data Book, 2024, Success Rates
NIH Institute and Center Budgets, FY2024 > Total NIH FY2024: $48.6B appropriation > National Cancer Institute (NCI): $7.22B (-1.3% from FY2023) > National Institute of Allergy & Infectious Diseases (NIAID): $6.56B (flat from FY2023) > National Institute on Aging (NIA): $4.5B+ ($90M for Alzheimer’s/dementia research) > — AIP: FY2024 NIH Budget | CRS: NIH Funding FY1996-FY2025 | NCI: FY2024 Appropriation
NIH research misalignment with public health outcomes > “Despite substantial funding, the United States lags behind other developed nations in key health metrics, such as life expectancy and infant mortality. > This discrepancy suggests a misalignment between NIH-funded research and tangible public health improvements.” > — Nature, 2011, US health reform: The NIH’s weak report card
NIH Office of the Director budget info > “Budget information and appropriations for the Office of the Director.” > — NIH, OD Budget
NIH organizational complexity > “The NIH’s expansion to 27 institutes and centers has led to a complex organizational structure… associated with increased administrative costs and potential inefficiencies in resource allocation.” > — National Academies Press, 2003, Enhancing the Vitality of the National Institutes of Health
NIH organizational statistics > Center for Scientific Review (CSR): Organizes review activities into Review Branches (RBs) containing study sections > Study Sections (Scientific Review Groups): Panels of experts reviewing and scoring NIH grant applications > Specific numbers (220+ study sections, 6,000+ employees, 80,000+ grant reviewers) not verified in current NIH sources > — NIH CSR: Study Sections | NIH CSR: Regular Standing Study Sections
Number of patient-treatments tested by NIH for its budget > ClinicalTrials.gov (NIH registry): 455,437 studies in all 50 states, 221 countries (as of March 2025) > Interventional clinical trials: 404,637 trials (as of March 2025) > Clinical trial data (2000-2015): 406,038 trial entries for 21,143 compounds > Specific “658,000” figure not found in current NIH sources > — ClinicalTrials.gov | PMC: Clinical Trial Landscape 2000-2020
NIH peer review penalizes risk > “The NIH peer review system disproportionately funds safe, incremental research over high-risk, high-reward proposals.” > — Federation of American Scientists, Supercharging Biomedical Science at the NIH
NIH RECOVER Initiative inefficiency > “The RECOVER initiative has a total allocated budget of over $2.3 billion. > While major interventional trials like RECOVER-VITAL and RECOVER-NEURO closed enrollment in mid-2025, no results have been published as of late 2025.” > — RECOVER Initiative & News Reports, 2025, Official Site
NIH SBIR grant success rate (9.9%) > “The NIH SBIR Phase I success rate fell to 9.9% in 2024.” > — LinkedIn, Kirk Macolini, 2024, NIH SBIR STTR activity
NIH spending per FDA-approved drug (adjusted) > “The average NIH investment per FDA-approved drug from 2010-2019 was $711 million, after adjusting for research spillovers where one study benefits multiple drugs.” > — Bentley University, 2022, New Study Shows NIH Investment in New Drug Approvals
Death toll from famine in North Korea > 1990s North Korean famine (“Arduous March”): 1995-2000 period of mass starvation > Death toll estimates vary widely: 240,000 to 3.5 million deaths from starvation/hunger-related illnesses > High-end estimates: Andrew Natsios estimated 2.5-3.5 million deaths (1994-1999 peak period) > Conservative estimates: 600,000-1 million deaths (3-5% of pre-crisis population) > U.S. Census Bureau (2011): 500,000-600,000 excess deaths (1993-2000) > Peak deaths: 1997; flooding followed by drought (1995-1997) caused food availability collapse > — Wikipedia: 1990s North Korean Famine | National Interest: 3.5 Million Dead | USIP: Politics of Famine
NSF grant freezes (news report) > “NSF freezes payments in response to executive actions.” > — NPR, 2025, NSF freezes payments
The Nuclear Disarmament “Freeze” Movement of the 1980s > Mass U.S. movement (1980s) to halt testing, production, deployment of nuclear weapons between U.S. and Soviet Union > Origins: Proposed by Randall Forsberg (Dec 1979); Nuclear Weapons Freeze Campaign formed March 1981 at Georgetown University > June 12, 1982: ~1 million people rallied in NYC (largest peacetime rally in U.S. history) > 1983: Congress passed nuclear freeze resolution > Impact: Reagan administration reversed rhetoric (“nuclear war cannot be won and must never be fought”) > Major support: Religious community (National Council of Churches, Protestant denominations, progressive evangelicals, African-American churches) > 1987: Merged with Committee for a Sane Nuclear Policy → formed Peace Action > — Wikipedia: Nuclear Freeze Campaign | Arms Control: Nuclear Freeze and Its Impact | Pace: Nuclear Freeze Campaign 1970s-1980s
Nuclear Extinction Events (Estimated 10-100 winter scenarios) > Feynman: 13,000 warheads / 100-1000 per major exchange (US-Russia ~5,000 each) = 2-13 full wars; regional (50-100) = 130-260. > Winter threshold ~50-150 Tg soot. > — Based on FAS arsenal data and climate models
Nuclear Winter Famine > “We estimate that a nuclear war between the United States and Russia would produce 150 Tg of soot and lead to ~5 billion people dying at the end of year 2.” > — Xia et al., Nature Food, 2022, Global food insecurity and famine from nuclear war soot injection
Estimated number of known human diseases > Rare diseases: ~8,000 named rare diseases, with 100+ new ones characterized yearly > ICD-11 Foundation: ~80,000 entries (diseases, syndromes, health phenomena) + 40,000 synonyms > ICD-10 rare disease coverage: <500 rare diseases, only ~240 with specific codes (<3% of rare diseases) > ICD-11 rare disease coverage: 5,400-5,500 rare diseases from Orphanet database (10X improvement over ICD-10) > Research dataset: 6,519 rare diseases analyzed in coverage studies > — WHO: Rare Diseases FAQ | Orphanet: Rare Diseases in ICD11 | PMC: Rendering of Human Phenotype in ICD-11
Obesity Epidemic Statistics > “The US obesity prevalence was 42.4% in 2017-2018, and the prevalence of severe obesity increased from 4.7% to 9.2%.” > — CDC, 2020, Link
Occupy Wall Street Movement (2011) > Left-wing populist movement against economic inequality, capitalism, corporate greed, big finance, money in politics > September 17 - November 15, 2011 (59 days) in Zuccotti Park, NYC Financial District > Slogan “We are the 99%” highlighted income/wealth inequality: Top 1% owned 40% of wealth, earned 20% of income (2011) > Organized by Adbusters (Kalle Lasn, Micah White); ended November 15 when police cleared park (~200 arrested) > Legacy: Successfully reframed national conversation about economic inequality in simple, effective terms > — Wikipedia: Occupy Wall Street | Britannica: Occupy Wall Street | History: Occupy Wall Street Begins
Odds of a single vote being decisive in a U.S. presidential election > National average: 1 in 60 million chance (2008 election analysis by Gelman, Silver, Edlin) > Swing states (NM, VA, NH, CO): ~1 in 10 million chance > Non-competitive states: 34 states >1 in 100 million odds; 20 states >1 in 1 billion > Washington DC: 1 in 490 billion odds > Methodology: Probability state is necessary for electoral college win × probability state vote is tied > — Columbia/NBER: What Is the Probability Your Vote Will Make a Difference? | Economic Inquiry 2012
Office of the National Coordinator for Health Information Technology (ONC) > Now: Office of the Assistant Secretary for Technology Policy/ONC (ASTP/ONC) - within HHS Office of the Secretary > Mission: Coordinate nationwide efforts for advanced health IT and electronic health information exchange > Created: April 27, 2004 by President Bush (Executive Order 13335) > Mandated by Congress: 2009 Health Information Technology for Economic and Clinical Health Act (HITECH Act, part of ARRA) > Focus: Data, technology, interoperability, AI strategies and policies for HHS > — Wikipedia: ONC | HHS: ASTP/ONC | HealthIT.gov
Median oncologist salary > 2024 average compensation: $464,000 (medical oncology), well above average U.S. specialist salary of $394,000 > Radiation oncology: Frequently exceeds $472,000/year > Hematology-Oncology: $450,000-$516,017 (MGMA median) > High-demand states (SD, NH, ND): Often >$500,000 due to rural workforce shortages > Locum tenens: $200-$250/hour > — Weatherby: Medical Oncologist Salary 2024 | Sermo: Oncologist Salaries 2025 | AMN Healthcare: Oncologist Salary 2025
Open-source and platform-as-a-service multi-trillion dollar market > Open source services market: $30.2B (2023) → $81.4B (2030) at 16.5% CAGR; other estimates $135.9B by 2033 > Open source cloud platform: $6.23B (2024) → $18.12B (2033) at 12.8% CAGR > Platform as a Service (PaaS): Growing at 12.6% CAGR > Broader cloud computing market: Projected $1.5 trillion by 2033 at 15% CAGR > Current market in tens of billions, approaching multi-trillion valuations in long term > — Grand View Research: Open Source Services Market | Precedence Research: Open Source Services Market
OpenTrials Database Initiative > Collaborative open database for all structured data/documents on all clinical trials > Launched: October 10, 2016 beta at World Health Summit > Director: Dr. Ben Goldacre (University of Oxford DataLab, author of Bad Science/Bad Pharma, AllTrials campaign founder) > Collaboration: Open Knowledge International + Oxford DataLab; funded by Laura and John Arnold Foundation > Features: Threads together registry entries, journal papers, regulatory docs, systematic reviews, clinical study reports, consent forms, protocols > Goal: Increase discoverability, identify inconsistent data, enable audits, support advocacy for better data, drive up open data standards > — OpenTrials: Official Site | Trials: OpenTrials Article | Open Knowledge Blog
Elinor Ostrom’s work on cooperation vs. punishment > Ostrom demonstrated cooperative management of natural resources can preserve (not degrade) them; trust between strangers can be established as basis for collaborative common-pool resource management > Pioneering experiments confirmed widespread use of costly punishment in response to excessive resource extraction > Showed power of communication and critical role of informal agreements in supporting cooperation > Public goods game experiments: 70-80% cooperation thresholds achievable with leader support systems (vs. none without support) > Provided sharp critique of free-rider problem arguments from within mainstream economics > — ResearchGate: Ostrom’s Contributions to Experimental Study of Social Dilemmas | Jacobin: The Economist Who Solved the Free-Rider Problem
Pandemic vs. war deaths comparison > “COVID-19 deaths: over 7 million confirmed deaths” vs. annual conflict deaths typically under 100,000. > — Our World in Data, 2024, COVID-19 Deaths
Over 50 million parents of sick children > Children with special health care needs (CSHCN): 14.6M children (19.8% of American children) > Chronic conditions: ~43% of US children (32M) have at least 1 of 20 chronic conditions; 54.1% when including overweight/obesity/developmental delays > Recent rise: Nearly 1-in-3 young people (25M ages 5-25) now living with chronic condition/functional limitation > Impact on parents: Increased stress, families more likely to experience poverty and poor health > — UCLA Health: Pediatric Chronic Disease Prevalence | PMC: Health Outcomes of Parents | Documenting Hope: Statistics
Patient enrollment rates in clinical trials > Overall enrollment: 5-8% of adult cancer patients (historically <5%, recent data shows 7.1%) > When offered participation: 55% of patients agree to enroll > Gap caused by: Structural barriers (half of patients), eligibility exclusions (half of remaining), physicians not offering > Physician referral rate: Median 5 patients/year (<0.2% of annual patient volume) > Conclusion: Low enrollment not primarily due to patient refusal, but lack of opportunity > — Applied Clinical Trials: Rebooting the 5% Statistic | JNCI: When Offered to Participate | JCO: National Estimates
Patient willingness to participate in clinical trials > Recent surveys: 49-51% willingness (2020-2022) - dramatic drop from 85% (2019) during COVID-19 pandemic > Cancer patients when approached: 88% consented to trials (Royal Marsden Hospital) > Study type variation: 44.8% willing for drug trial, 76.2% for diagnostic study > Top motivation: “Learning more about my health/medical condition” (67.4%) > Top barrier: “Worry about experiencing side effects” (52.6%) > — Trials: Patients’ Willingness Survey | CenterWatch: Willingness Drops Dramatically | PMC: Study Design Factors
PatientsLikeMe Patient Advocacy Group > Founded: 2004 (launched 2006 for ALS patients); free online network for chronic disease patients > Community: 500,000+ members across multiple conditions (ALS, MS, Parkinson’s, fibromyalgia, HIV, epilepsy, mood disorders, organ transplant, etc.) > Features: Patient-reported outcomes, symptom tracking, social features; all members can see each other’s data, view aggregated reports, identify “patients like them” > Key differentiator: Emphasis on structured quantitative data aggregated for research purposes > Patient benefits: 72% found site helpful learning about symptoms; 57% for understanding treatment side effects; 42% for finding similar patients > — Wikipedia: PatientsLikeMe | PMC: Scaling PatientsLikeMe | PatientsLikeMe
Patrick Soon-Shiong’s focus on cancer research > Billionaire biotech entrepreneur (net worth $12B, 2025); founder of NantWorks (healthcare/biotech/AI startups) > Key achievements: Invented Abraxane (FDA-approved for metastatic breast, lung, advanced pancreatic cancer); first drug in 20+ years showing significant survival improvement for metastatic pancreatic cancer > Recent breakthrough: Anktiva (new immunotherapy class) FDA-approved April 2024 for non-muscle invasive bladder cancer; 71% complete remission, 24.1 median duration > Companies: Executive Chairman of NantKwest (immunotherapy, natural killer cells); Chairman/CEO of ImmunityBio (vaccines/immunotherapy for cancer/infectious diseases) > 2016 Cancer Moonshot: Goal to enroll 20,000 patients in trials, develop effective vaccine by 2020 (faced criticism, fell short of goals) > — Wikipedia: Patrick Soon-Shiong | STAT: Soon-Shiong Cancer Therapy | BioSpace: Cancer Moonshot Progress
Passage of the USA PATRIOT Act > Introduced: October 23, 2001 by Rep. Jim Sensenbrenner (R-WI) as H.R. 3162 > Passed House: October 24, 2001 (357-66 vote, Democrats majority of “no” votes) > Passed Senate: October 25, 2001 (98-1 vote, only Russ Feingold D-WI voted “no”) > Signed into law: October 26, 2001 by President George W. Bush > Length: 342 pages, passed hastily without public opportunity for review > ACLU concern: Senate forced to vote on legislation it hadn’t had opportunity to read (offices closed, staff couldn’t access papers) > — Wikipedia: Patriot Act | Britannica: USA PATRIOT Act | ALA: Chronology of USA PATRIOT Act
Prescription Drug User Fee Act (PDUFA) > Passed: 1992 by Congress; authorizes FDA to collect fees from drug manufacturers to fund new drug approval process > Purpose: Shorten time from manufacturer submission (NDA/BLA) to FDA decision; address sizeable backlog of drug applications > Fee types (each 1/3 of total): Application review fees, establishment fees (annual per facility), product fees (annual per product) > Impact: Approval time fell significantly from ~31.3 months (pre-PDUFA) during 1993-1996 > Reauthorizations: Every 5 years - PDUFA II (1997), III (2002), IV (2007), V (2012), VI (2017), VII (2022) > Financial shift: FY1993 user fees = 7% of program costs; FY2023 user fees = 75% of program costs > — Wikipedia: PDUFA | FDA: PDUFA | PMC: PDUFA More Than User Fees
Private Equity Military Sector Returns > “Top-quartile private equity funds focused on the aerospace and defense sector often target an internal rate of return (IRR) of 20-30% for their investors.” > — PitchBook & Industry Analysis, 2024, Link
Token Safe Harbor concept (Peirce 2.0) > “The safe harbor seeks to provide network developers with a three‑year grace period… to facilitate participation in, and the development of, a functional or decentralized network.” > — Hester M. Peirce, SEC Commissioner, 2021, Token Safe Harbor 2.0
Fiduciary Duty of Pension Funds to Maximize Returns > No explicit ERISA duty to maximize returns: “No authority requiring a plan fiduciary to pick the best-performing fund” (8th Circuit, Meiners v. Wells Fargo) > Core ERISA duties instead: (1) Duty of Loyalty - act solely in interests of participants/beneficiaries; (2) Duty of Prudence - act prudently in decision-making process; (3) Risk-adjusted return analysis > Focus: Process over results - investments don’t have to be “winners” if part of prudent diversified portfolio > Standard: Fiduciaries must follow prudent process, not achieve specific performance outcomes or maximum returns > — Harvard Corp Gov: Fiduciary Duties | DOL: Meeting Fiduciary Responsibilities | IRS: Retirement Plan Fiduciary Responsibilities
Pentagon audit failures ($2.46T unaccounted) > “In the most recent audit, the Department of Defense (DoD) could not account for approximately 60% of its $4.1 trillion in assets, amounting to $2.46 trillion unaccounted for.” > Alternative title: Pentagon unsupported accounting adjustments ($6.5T, single year, US Army) > “In 2015, the Department of Defense’s Inspector General reported that the Army could not adequately support $6.5 trillion in year-end adjustments, indicating severe accounting discrepancies.” > — The Commune, 2024, Pentagon Misplaced $2.46 Trillion | Accounting Magazine, 2016, Audit: Pentagon Cannot Account for $6.5 Trillion Dollars
Per Capita Lifetime Cost of Violence (Estimated ~$170,000) > Feynman: Annual global cost $16.5T / 8B people = $2,062/year * 80 years = ~$165,000. > — Based on IEP Global Peace Index
$74,259 per person lifetime savings from conflict reduction > Calculation based on economic case for peace: War costs $74,259 per person over lifetime > Derived from global conflict costs ($300B lost human capital annually + broader $14T/year global violence/conflict costs) / population over 80-year lifespan > IEP Global Peace Index calculation: $16.5T annual global cost / 8B people = $2,062/year × 80 years = ~$165,000 lifetime cost > — Think by Numbers: War Costs $74,259/Lifetime | WEF: War Violence Costs $5/Day
Pharmaceutical industry lobbying statistics > Pharmaceutical and health products industry spent $388 million on federal lobbying in 2024 ($6.1 billion since 1999) > Employs roughly 3 lobbyists for every member of Congress > — OpenSecrets: Pharmaceuticals/Health Products > Note: The industry has consistently been among the top spenders on lobbying in Washington D.C., with major pharmaceutical companies like Pfizer, AbbVie, and PhRMA leading expenditures
Pharmaceutical spending on marketing research: $60 billion/year > Global pharma marketing (2022): $180B (nearly matching $188B R&D spending) > U.S. pharma marketing (2022): $90B (largest market) > 2019 survey: $402.3B spent on pharmaceutical marketing/advertising globally > 2023 U.S. spending: Top 10 companies spent $13.8B on advertising/promotion > Direct-to-consumer advertising: Record $7.6B (2022); TV ads $6.5B (2022); digital ads $3.1B (2023, +14% from 2022) > Physician marketing (detailing): $27B globally (2022) > Historical growth: $17.7B annually (1997) → $30B (2016), with $26.9B spent by drug companies in 2016 > — Statista: Pharma Marketing Spend | JHU: Consumer Advertising Spending | TechTarget: Big Pharma DTC Ad Spend
Pharmaceutical spending on actual novel cures: ~$20 billion > Total global pharma R&D (2023): >$300B; (2021): $276B actual investment (more than double commonly cited estimates) > Industry R&D (2019): $83B, 10X higher than 1980s (inflation-adjusted) > Top 15 pharma companies (2021): Record $133B R&D investment (+44% since 2016) > Individual example: J&J invests 20.9-22.8% of revenue in R&D ($9.5B-$11.9B annually) > Cost per novel drug: $318M to $2.8B estimates; total ecosystem investment per successful approval >$5B > ROI declining: Average projected ROI fell from 6.8% (2021) to 1.2% (2022) for top 20 companies > — Statista: Worldwide Pharma R&D | CBO: R&D in Pharmaceutical Industry | IQVIA: Global Trends in R&D 2023
Annual profits for pharmaceutical industry from treatment vs. cures > Global pharma market revenue: $1.5T (2022), $1.6T (2023), $1.77T (2025); projected $2.8-3.03T by 2032-2034 > U.S. pharma revenue: >$550B (2021) > Industry profits (2000-2018): 35 large pharma companies reported $11.5T cumulative revenue, $1.9T net income > 2022 profits: Major pharma companies made >$112B in profits (U.S. Senate Health Committee report) > Profit margins: Median 13.8% for pharma vs 7.7% for non-pharma S&P 500 companies; largest 25 companies 15-20% annual average vs 4-9% for non-drug companies > — Statista: Pharmaceutical Market Worldwide Revenue | PMC: Profitability of Large Pharma | Acumen: Pharmaceutical Market Size
Pharmaceutical industry annual profits > Net income (2000-2018): 35 large pharma companies earned $1.9T cumulative net income on $11.5T revenue > 2022 profits: Major pharma companies made >$112B in profits > Profit margins: Pharma companies 13.8% median vs 7.7% for other S&P 500 companies > Largest 25 companies: 15-20% annual average profit margin vs 4-9% for non-drug companies globally > Profitability: Pharma significantly more profitable than most S&P 500 companies > — PMC: Profitability of Large Pharmaceutical Companies | Bentley: Pharma More Profitable Than S&P 500 | GAO: Drug Industry Profits
Polypill for Primary Prevention Cost per QALY > “A polypill strategy was potentially cost-effective compared to other strategies for most sub-groups ranging from dominance to up to £18,811 per QALY depending on patient sub-group.” > — PLOS One, Link
Proof-of-Stake Energy Efficiency > Ethereum’s “Merge” (Sept 15, 2022): Transition from proof-of-work to proof-of-stake > Energy reduction: 99.9-99.95% less energy consumption (~2000X more energy-efficient) > Actual consumption drop: 23M megawatt hours/year → 2,600 megawatt hours/year > Carbon footprint: 99.992% reduction (11.016M tonnes CO2e → 870 tonnes CO2e) > — Ethereum Foundation: ETH Will Use 99.95% Less Energy | Ethereum.org: Energy Consumption | Decrypt: Energy Down 99.99% After Merge
Post-1962 drop in new drug approvals > 1962 Kefauver-Harris Amendment: Required proof of effectiveness (not just safety) before FDA approval > Impact: “New regulatory clampdown on approvals immediately reduced the production of new treatments by 70%” > Context: Regulatory response to thalidomide tragedy (late 1950s); drug caused birth defects in 46 countries but was already blocked in U.S. by existing FDA safety requirements > More than half of medicines available in 1962 were discontinued following implementation > Correlated effect: Lifespan growth declined from ~4 years/decade (pre-1962) to ~2 years/decade (post-1962) > — Think by Numbers: How Many Lives Does FDA Save? | Wikipedia: Kefauver-Harris Amendment | PMC: Lost Medicines
Post-1962 explosion in drug development costs > Cost to develop a new prescription drug: $2.6 billion (2014 Tufts study), increasing to $2.9 billion with post-approval development > Represents 145% increase (inflation-adjusted) from 2003 estimate of $802 million > Based on 106 drugs from 10 pharmaceutical companies tested between 1995-2007 > — Tufts Center for Study of Drug Development | C&EN: Cost of Drug Development > Note: This study has been controversial; some organizations like Doctors Without Borders suggest actual costs may be substantially lower. Deloitte 2023 report shows costs continuing to rise
Post-1962 slowdown in life expectancy gains > Pre-1962: Lifespan growth increased by ~4 years per decade > Post-1962: Lifespan growth declined to ~2 years per decade (50% reduction) > Correlation: Slowdown directly coincided with 70% reduction in new drug approvals following 1962 Kefauver-Harris Amendment > Context: Regulatory clampdown on approvals immediately reduced production of new treatments by 70% > — Think by Numbers: How Many Lives Does FDA Save?
Pre-1962 drug development costs and timeline > 1962 Drug Amendments significantly increased costs and timelines > Historical estimates (1970-1985): USD $226M fully capitalized (2011 prices) > 1980s drugs: ~$65M after-tax R&D (1990 dollars), ~$194M compounded to approval (1990 dollars) > Modern comparison: $2-3B costs, 7-12 years (dramatic increase from pre-1962) > Context: 1962 regulatory clampdown reduced new treatment production by 70%, dramatically increasing development timelines and costs > Note: Specific pre-1962 “$74M, 2-3 years” figures not verified in sources > — Think by Numbers: How Many Lives Does FDA Save? | Wikipedia: Cost of Drug Development | STAT: 1962 Law Slowed Development
Pre-1962 physician-led clinical trials > Pre-1962: Physicians could report real-world evidence directly > 1962 Drug Amendments replaced “premarket notification” with “premarket approval”, requiring extensive efficacy testing > Impact: New regulatory clampdown reduced new treatment production by 70%; lifespan growth declined from ~4 years/decade to ~2 years/decade > Drug Efficacy Study Implementation (DESI): NAS/NRC evaluated 3,400+ drugs approved 1938-1962 for safety only; reviewed >3,000 products, >16,000 therapeutic claims > FDA has had authority to accept real-world evidence since 1962, clarified by 21st Century Cures Act (2016) > Note: Specific “144,000 physicians” figure not verified in sources > — Think by Numbers: How Many Lives Does FDA Save? | FDA: Drug Efficacy Study Implementation | NAS: Drug Efficacy Study 1966-1969
$5.60 saved per $1 prevention > “An investment of $10 per person per year in proven community-based programs … could save the U.S. over $16 billion annually within five years, representing a return of $5.60 for every $1 invested.” > — Trust for America’s Health, 2008
Princeton study on policy outcomes and influence of elites vs. average citizens > Study by Martin Gilens (Princeton) and Benjamin I. Page (Northwestern): Analyzed 1,779 policy outcomes (1981-2002) > Finding: “Economic elites and organized groups representing business interests have substantial independent impacts on U.S. government policy, while average citizens have little or no independent influence” > Rich, well-connected individuals steer the country’s direction, regardless of or even against the will of the majority of voters > Note: Specific “78 percent” and “zero percent correlation” statistics not found in sources > — Princeton: Testing Theories of American Politics (PDF) | RepresentUs: US Oligarchy Research Explained | Internet Archive: Gilens and Page 2014
Cost reduction in principal-agent theory through incentive alignment > Agency theory explores conflicts between principals (shareholders) and agents (executives/managers) > When agent incentives align with principal objectives, agency costs reduce significantly > Steeper alignment of agent rewards with principal objectives = lower costs > Benefits of reducing agency costs can outweigh monitoring costs > Example: Energy efficiency study showed misaligned incentives caused 30% less electricity savings > Note: General “50-70% cost reduction” claim not verified in sources > — Wikipedia: Principal-Agent Problem | Inspired Economist: Agency Theory | AEA: The Costs of Misaligned Incentives
Psychological impact of war cost ($100B annually) > PTSD economic burden (2018 U.S.): $232.2B total ($189.5B civilian, $42.7B military) > Civilian costs driven by: Direct healthcare ($66B), unemployment ($42.7B) > Military costs driven by: Disability ($17.8B), direct healthcare ($10.1B) > Exceeds costs of other mental health conditions (anxiety, depression) > War-exposed populations: 2-3X higher rates of anxiety, depression, PTSD; women and children most vulnerable > Note: Actual burden $232B, significantly higher than “$100B” claimed > — PubMed: Economic Burden of PTSD | VA News: Study Economic Burden | PMC: Mental Health Costs Armed Conflicts
Public support for redirecting military spending to health > >70% of voters said their community would struggle temporarily/recover or that Pentagon cuts would have no local impact > 2-to-1: Voters agreed “U.S. should cut Pentagon spending to invest more in healthcare, education, infrastructure, clean energy that create more jobs” > 57% supported cutting defense budget 10% if funding reallocated to CDC and pressing domestic needs (July 2020) > 67% of Americans want to expand federal budget for healthcare (2024) > Healthcare ranks #1 priority for increased funding (23%), military ranks 5th (11%) > — The Nation: Americans Want Jobs Not War | Data for Progress: Cut Pentagon Budget | Chicago Council: Americans Prioritize Domestic Spending
Publication rate of clinical trial results > ~50% of clinical trials never publish results (NHS-funded systematic review, 2010) > Schmucker et al (2014): 53% of trials published (analyzing 39 studies, >20,000 trials) > Munch et al (2014): 46% of pain treatment trials published > Chang et al (2015): 49% of high-risk cardiac device trials published > Positive findings: 3X more likely to be published than negative results > Antidepressant example: Published literature showed 94% positive trials; FDA analysis showed only 51% positive > — AllTrials: Half of Trials Unreported | Nature: Half of US Trials Go Unpublished | PMC: Publication Bias in Clinical Trials
QALY definition and use > “The quality-adjusted life year (QALY) is the academic standard for measuring how well all different kinds of medical treatments lengthen and/or improve patients’ lives, and therefore the metric has served as a fundamental component of cost-effectiveness analyses in the US and around aound the world for more than 30 years.” > — ICER
$100,000–$150,000 per QALY > “Health benefit price benchmark (HBPB) will be reported using standard range from $100,000 to $150,000 per evLYG and QALY” > “The range for threshold prices used to determine ICER health benefit price benchmarks remains $100,000-$150,000 per evLYG and per QALY” > — ICER Reference Case | ICER Value Assessment Framework
Global prevalence of rare diseases: 400 million > Estimates range: 263-446 million people (some sources cite ~400M) > Conservative estimate: 300 million (widely cited) > Analysis based on 3,585 rare diseases = 3.5-5.9% of global population > Excludes rare cancers/infectious diseases, actual number likely higher > — Global Genes: 300M+ Worldwide | AJMC: Not So Rare
Raytheon annual revenue > RTX Corporation (formerly Raytheon Technologies): $80.8B sales (2024), up 9% from 2023 > 2023: $68.92B revenue > Merger: 2020 with United Technologies; renamed RTX Corporation July 2023 > Segments: Collins Aerospace (34%), Pratt & Whitney (34%), Raytheon Intelligence & Space (32%) > Note: $42B figure outdated; current revenue ~$80B > — RTX: 2024 Results | Wikipedia: RTX Corporation | Statista: Raytheon Revenue 2008-2024
Reconstruction costs from active conflicts > Individual conflict examples: Libya, Syria, Yemen ~$300B combined (World Bank) > Syria alone: $250B-$1T estimates > Ukraine: >€500B reconstruction costs > Gaza: $18.5B infrastructure damage > Global conflict/violence cost: $14.3T/year (2016, includes military spending, security, losses) > Note: Specific “$1,875B for 47 conflicts” figure not verified in sources > — IMF: Cost of Conflict | WEF: Conflict Costs $14T/Year | Fortune: Ukraine $1T Reconstruction
RECOVER Initiative budget update (>$2.3B) > “The $662 million in funds will be allocated over Fiscal Years 2025-2029 to support the following research areas: RECOVER-TLC clinical trials…” > — RECOVER Initiative, 2024, NIH Adds Funds to Long COVID Research
NIH RECOVER Initiative patient enrollment numbers > Enrolled: ~30,000 people in ongoing studies and clinical trials > Goal: 40,000 adults and children > $1.15B effort (including American Rescue Plan Act 2021 support) > One of largest, most diverse Long COVID cohorts in world > — NIH: RECOVER Initiative Enrollment | RECOVER: Long COVID Clinical Trials
RECOVER Initiative trial status update > “NIH RECOVER expects to have VITAL and NEURO trial results available by late 2025 or early 2026.” > — The Sick Times, 2025, Live Blog: RECOVER-TLC Workshop
RECOVERY Trial Cost per Patient > “The RECOVERY trial, for example, cost only about $500 per patient… By contrast, the median per-patient cost of a pivotal trial for a new therapeutic is around $41,000.” > — Oren Cass, Manhattan Institute, 2023, Slow, Costly Clinical Trials Drag Down Biomedical Breakthroughs
RECOVERY trial global lives saved > Dexamethasone saved ~1 million lives worldwide (by March 2021, 9 months after discovery) > UK alone: 22,000 lives saved > June 2020 announcement: Dexamethasone reduced deaths by up to 1/3 (ventilated patients), 1/5 (oxygen patients) > Impact immediate: Adopted into standard care globally within hours of announcement > — NHS England: 1 Million Lives Saved | Pharmaceutical Journal: 1M Lives Saved | RECOVERY Trial: Dexamethasone Result
RECOVERY trial 82x cost reduction > RECOVERY trial: ~$500 per patient ($20M for 48,000 patients = $417/patient) > Typical clinical trial: ~$41,000 median per-patient cost > Cost reduction: ~80-82X cheaper ($41,000 ÷ $500 ≈ 82X) > Efficiency: $50 per patient per answer (10 therapeutics tested, 4 effective) > Dexamethasone estimated to save >630,000 lives > — Manhattan Institute: Slow Costly Trials | PMC: Establishing RECOVERY at Scale
RECOVERY Trial Dexamethasone Results > “Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; \(p=0.0003\)) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; \(p=0.0021\))” > — RECOVERY Trial, Link
RECOVERY Trial efficiency > “At a cost of $20 million for 48,000 patients, the RECOVERY trial cost about $500 per patient… that is about $50 per patient per answer.” > — Professor Martin Landray (co-chief investigator), quoted in Oren Cass, Manhattan Institute, 2023, Slow, Costly Clinical Trials Drag Down Biomedical Breakthroughs
RECOVERY Trial Summary Quote > “One trial. > Over 47,000 participants. > Nearly 200 hospital sites, across six countries. > Ten results. > Four effective COVID-19 treatments… > Through discovering four treatments that effectively reduce deaths from COVID-19, it is certain that the study has saved thousands – if not millions – of lives worldwide.” > — Oxford University News, Link
Refugee lost annual earning potential ($23,400) > Refugee economic impact: Net positive $123.8B fiscal impact (2005-2019, 15 years) > Refugees pay $21K more in taxes than benefits received over first 20 years in U.S. > Earnings gap: Refugees work at higher rates than natives but earn less; never reach U.S.-born earning levels > Income progression: <5 years in U.S. = $30,500 median; 20+ years = $71,400 (exceeds national $67,100 median) > Note: Specific “$23,400 lost earning potential” figure not verified in sources > — ASPE: Fiscal Impact of Refugees | American Immigration Council: Economic Impact | NBER: Economic Outcomes of Refugees
Milestones in Regenerative Medicine and Tissue Engineering > 1999: First 3D-printed organ (bladder) transplanted into human (Wake Forest Institute, still functioning 20+ years later) > Windpipes (trachea): 3D-printed windpipe transplants performed; patient received biodegradable 5-year windpipe > Blood vessels, skin: Mobile bioprinters can print skin directly onto wounds at patient bedside > Tubular organs: Urine conduits engineered and implanted in patients > 3D-printed ear implant: World’s first successfully transplanted > Current status: Can print flat structures (skin), tubular (blood vessels), hollow non-tubular (bladder); complex life-sized organs 20-30 years away > — Wake Forest: Record of Firsts | Built In: 3D-Printed Organs | PMC: 3D Bioprinting for Organ Regeneration
Salary increases for regulators after entering private industry > FDA revolving door documented: 27% of hematology-oncology drug reviewers (2001-2010) left for industry; 57% of those who left worked/consulted for biopharmaceutical industry > 9 out of 10 FDA commissioners moved to pharmaceutical companies (2006-2019) > Salary differences: FDA medical officer $73,846-$133,444; pharma executives averaged >$163,000 (2015); private sector offers significantly higher salaries > “Leaving FDA for industry can bring a major salary bump” > Note: Specific “400%” increase not verified in sources > — Science: FDA’s Revolving Door | NPR: How Revolving Door Spins | RAPS: Revolving Door Continues
Research to practice gap (17 years) > “It takes an average of 17 years for new scientific evidence to be implemented into clinical practice.” > — JAMA, 2023, Mind the 17-Year Gap
Annual deaths from respiratory disease > Chronic respiratory diseases: 4.0 million deaths annually (2019) > COPD specifically: 3.5 million deaths (2021) - 4th leading cause of death globally > Pneumonia: 2.5 million deaths including 672,000 children (2019) > Combined respiratory deaths: ~6.5 million annually > — WHO: COPD Fact Sheet | Global Burden of Disease: Respiratory Diseases 2019 > Note: 90% of COPD deaths in those under 70 occur in low- and middle-income countries. COPD affects over 380 million people globally
Reversal of Aging in Mice at David Sinclair’s Lab > Harvard Medical School (Sinclair lab): Breakdown in epigenetic information causes mice to age; restoring epigenome integrity reverses aging signs > “ICE” mouse model: Induces DNA breaks, drives epigenetic changes, accelerates aging > OSK therapy (Oct4, Sox2, Klf4): Three Yamanaka factors delivered to rewind mature cells to earlier state > Results: Organs/tissues resumed youthful state; vision restored in glaucoma mice (first successful reversal, not just halting progression) > Information Theory of Aging: “Aging is information lost in cells, not just damage accumulation”; reversibility proves “system is intact, backup copy exists, software needs rebooting” > Published: Cell, January 2023 > — HMS: Loss of Epigenetic Information | Science: Two Teams Reverse Aging in Mice | Time: Key Milestone in Reversing Aging
Number of patients helped by the U.S. Right to Try Act > 2018-2022: Supported access to only 12 products total; 4 products in 2023 > Number of people treated: Not publicly reported, “likely only in the hundreds” > Specific documented cases: 75+ neuroendocrine cancer patients (LU-177); at least 1 ALS patient (NurOwn); 7 glioblastoma patients (Gliovac) > Minimal safety reporting: Only annual basis, no requirement to publish results/outcomes > — PMC: Understanding Right to Try | STAT: Right to Try Hasn’t Helped | Healio: Well-Intentioned But Misguided
Right to Try Act Eligibility Requirements > Requires “life-threatening disease or condition” (not just “terminal”) > Life-threatening defined: “Diseases/conditions where likelihood of death is high unless course is interrupted” (21 CFR 312.81) > Additional requirements: Exhausted approved treatments, unable to participate in clinical trial, written informed consent > Drug must: Complete Phase 1 trial, be in active development, not FDA-approved for any use, have IND application filed > Note: More restrictive than Expanded Access (which also covers serious chronic diseases) > — PMC: Understanding Right to Try | FDA: Right to Try Fact Sheet | Congress: Right to Try Act
Russia medical research spending: $800 million > Agency for Strategic Initiatives (ASI): RUB 800M (~USD $11M, 2014-2020) for innovation development > NTI (National Technology Initiative): RUB 1,578M (~USD $21.5M, 2019-2020) for pandemic-related healthcare > HealthNet roadmap: Focuses on personalized medicine, life expectancy, prevention/treatment > Note: “$800M” appears to be RUB 800M (≈ $11M USD) for ASI over 6 years, not $800M USD annually > — Frontiers: Promoting Biomedical Communication in Russia | WHO: Health R&D Funding by Country
Russia’s Share of Global Military Spending > 2024: $149B military spending (5.5% of global $2,718B), 3rd largest spender globally > 38% increase from 2023; doubled since 2015 > 7.1% of Russia’s GDP, 19% of all Russian government spending > Top 5 spenders (US, China, Russia, Germany, India): $1,635T combined (60% of global) > Note: Russia accounts for ~5.5% of global military spending, not 10% > — SIPRI: 2024 Military Expenditure | SIPRI Fact Sheet 2024
Russia annual nuclear weapons spending: $65 billion > Nuclear weapons spending: $8.3B (2023), $9.6B (2022), $8.6B (2021), ~$10B (2016) > 3rd largest nuclear spender (after US, China) > 2016: 13% of total military spending > Note: “$65B” refers to Russia’s total military budget (not nuclear-specific); actual nuclear spending ~$8-10B annually > — SIPRI: How Much Does Russia Spend on Nuclear Weapons? | Statista: Nuclear Weapons Spending | ICAN: Wasted 2022 Report
Science & Tech Community > US STEM workforce: 36.8 million workers (2023), 24% of total employment > Healthcare practitioners/technical: 10.5M; Computer/mathematical: 6.1M; Engineers: 2.0M; Life/physical/social science: 1.6M > STEM employment growing 11% (2023-2033) vs 4% overall employment > Global estimates vary widely; specific “100 million” figure not verified in authoritative sources > — NSF: STEM Workforce 2023 | BLS: STEM Occupations
SEC Definition of an Accredited Investor > Individual: $1M net worth (excluding primary residence) OR $200K annual income ($300K joint) > Entity: $5M+ in assets; all equity owners are accredited; knowledgeable employees of private funds > Updated 2020: Includes professional certifications (Series 7, 65, 82) and “knowledgeable employees” > — SEC: Accredited Investor Definition | SEC: Updated Investor Definition 2020
SEC Form D Filing Requirement > Form D must be filed within 15 calendar days after the first sale of securities in Regulation D offering > Electronic filing required via EDGAR; state blue sky filings may also be required > Amendments required for material changes or additional sales beyond initial filing > — SEC: Form D | SEC: Form D Overview | Investopedia: SEC Form D
SEC innovation-friendly guidance (2025) > Project Crypto launched July 31, 2025: Commission-wide initiative to modernize securities rules for blockchain/“on-chain” markets > Innovation exemption rulebook: Chairman Atkins working toward new rules by end 2025/Q1 2026 > Token classification guidance: April 10, 2025 statement on crypto asset securities disclosure requirements > Crypto Task Force: Led by Commissioner Hester Peirce; shift from “regulation-by-enforcement” to facilitation > Interim relief: Staff instructed to use interpretive/exemptive relief while developing regulations > — Sidley: Project Crypto | CoinDesk: Innovation Exemption | SEC: Crypto Task Force
Investor Limits for Private Offerings > Rule 506(b): Unlimited accredited investors + up to 35 non-accredited investors (must be sophisticated) > Rule 506(c): Unlimited accredited investors only (allows general solicitation) > No “99 investor” maximum exists under Regulation D > Both Rule 506(b) and 506(c): Unlimited capital can be raised > — SEC: Rule 506(b) | Cornell Law: Rule 506 | Investor.gov: Rule 506
SEC Regulation A (Reg A) overview and cap ($75M/yr) > “Regulation A provides an exemption from the registration requirements… for offerings of securities up to $75 million in a 12‑month period, subject to eligibility, disclosure, and reporting requirements.” > — U.S. SEC, Regulation A Overview
SEC Regulation Crowdfunding (Reg CF) > “Regulation Crowdfunding enables eligible companies to offer and sell securities through crowdfunding.” > — U.S. SEC, Regulation Crowdfunding
SEC Regulation Crowdfunding (Reg CF) Raise Limit > Maximum: $5 million in 12-month period (as of March 15, 2021) > Increased from $1.07 million (nearly 5X increase) > Requirements: All transactions via SEC-registered intermediary (broker-dealer or funding portal); File Form C with SEC > Securities generally cannot be resold for one year > — SEC: Regulation Crowdfunding | Republic: SEC Raises Reg CF to $5M | Williams Mullen: SEC Finalizes New Limits
SEC Regulation D for accredited investors > Private placement exemption allowing companies to raise unlimited capital from accredited investors > Rule 506(b): Unlimited accredited + up to 35 non-accredited; no general solicitation > Rule 506(c): Only accredited investors; allows general solicitation/advertising > Form D filing required within 15 days of first sale > Investors receive restricted securities (resale limitations) > — SEC: Private Placements Rule 506(b) | Investor.gov: Rule 506 | Wikipedia: Regulation D
SEC Regulation S for non-U.S. investors > Exemption from SEC registration for securities offerings made outside the United States > Requirements: (1) Offshore transaction - offer not made to U.S. person, buyer outside U.S.; (2) No directed selling efforts in U.S. > Allows companies to raise capital from non-U.S. investors without wealth/sophistication requirements > Cannot be used to circumvent registration requirements; must be made in good faith > — Fourscore Law: Regulation S | Brinen Law: Regulation S | Deloitte DART: Regulation S
The Selfish Gene Quote > “We are survival machines, robot vehicles blindly programmed to preserve the selfish molecules known as genes.” > — Richard Dawkins, 1976, The Selfish Gene
Typical duration of outcome tracking in clinical trials > Median approach: Calculate endpoints when 50% of subjects reach endpoint (rather than waiting for all) > Duration of Response (DOR): Common secondary endpoint in oncology; median times vary widely > Examples: Survival median 5-8.2 months; DOR medians 16.4-19.4 months; CAR-T time to HSCT median 7.7 months (range 2-39 months) > Short-term endpoints often used for faster results; long-term outcomes may not be tracked > — PMC: Duration of Response Endpoint | Wikipedia: Clinical Endpoint | arXiv: Duration of Response in Oncology
Global military spending ($2.72T, 2024) > “In 2024, world military expenditure reached $2.718 trillion, marking a 9.4% increase from the previous year.” > — SIPRI, 2025, Trends in World Military Expenditure 2024
South Korea medical research spending > 2024: Basic research 2.63 trillion won (~$2 billion), grew 2% > Korean ARPA-H launched: 48.5 billion won initial funding; backers seek 1.9 trillion won over 10 years for high-risk biomedical studies > Overall R&D dropped 8% to 28.6 trillion won ($22B) in 2024 > Healthcare R&D subsidies cut 24% in 2023 despite being designated future growth engine > — Science: South Korea Proposes Cutbacks | Statista: South Korea R&D Expenditure | Korea Biomed: Healthcare R&D Cut
Smallpox Eradicated > “Following a successful global eradication campaign, the World Health Assembly officially declared the world free of smallpox in 1980.” > — WHO, Smallpox Overview
Smallpox Eradication ROI > “Adding up, the benefit–cost ratio for the entire world would have been about \(((\$350 + \$1070) \div 0.03)/\$298 \approx 159:1\). > These are huge numbers.” > “Smallpox Eradication: Model for Global Cooperation.” > — PMC3720047, Link | CSIS, Smallpox Eradication Model: Global Cooperation
George Soros’s 1992 Bet Against the British Pound > Black Wednesday (September 16, 1992): Soros assembled $10 billion short position against British pound > Increased position from $1.5B to $10B that morning; bought German marks while selling pounds > Profit: Over £1 billion ($1-1.5 billion) in single day > UK Treasury cost: £3.3 billion; Bank of England spent $29 billion trying to defend pound > Pound fell 15% vs. German mark, 25% vs. dollar; UK forced to exit European Exchange Rate Mechanism > Earned Soros title “the man who broke the Bank of England” > — Yahoo Finance: British Pounding | Wikipedia: Black Wednesday | The Balance: Black Wednesday
The South Sea Bubble of 1720 > South Sea Company founded 1711 as public-private partnership to consolidate national debt > Granted monopoly (Asiento de Negros) to supply African slaves to South America (1713) > Stock price explosion: £128 (Jan 1720) → £175 (Feb) → £330 (Mar) → £550 (May) → £1,000 (Aug) > Reality: No realistic prospect of trade; Company never realized significant profit from monopoly > Collapse: By September market crashed; December shares down to £124 > Called world’s first financial crash, first Ponzi scheme, classic “group think” speculation mania > Story disconnected from actual (negligible) profits > — Historic UK: South Sea Bubble | Wikipedia: South Sea Company | Britannica: South Sea Bubble
Death toll of Soviet Collectivization Famine (1930-33) > Soviet famine 1930-1933: 5.7-8.7 million deaths across Soviet Union (scholarly consensus) > Ukraine (Holodomor): 3.5-7 million; Most detailed demographic studies estimate 3.9 million > Range across sources: 5-10 million depending on methodology > Higher estimates (7-10M for Ukraine specifically): Ukrainian politicians cite these; historians note no precise figure possible due to Soviet census problems > Note: Original claim “1932-33” period too narrow; broader famine was 1930-33 > — Wikipedia: Soviet Famine 1930-33 | Wikipedia: Holodomor | Britannica: Holodomor
Soviet computer technology lag behind the West > Lag varied: T-5 tabulator 15-20 years behind; 7 years behind in mid-1970s; late 1980s Soviet computers comparable to early 1970s Western models > Programmers lagged 6-8 years behind American counterparts > Committee-based bureaucratic design: Uncoordinated government ministries; five-year plans from bureaucratic managers lacking technical know-how > Political decisions overrode scientist/engineer opinions in selecting technology cores > Copying Western hardware + international isolation + industrial structure = expanding lag through 1980s > Lack of common standards for peripherals and digital storage capacity caused significant lag > — Wikipedia: Computing in USSR | The Waves: Soviet Computer Failure | CyberNews: Why Soviets Didn’t Start PC Revolution
Soviet famine death toll estimates > 1930-1933 famine: 5.7-8.7 million deaths (scholarly consensus) > Some sources cite range of 5-10 million > Higher estimates: Robert Conquest estimated “at least 7 million” in European USSR; some claim ~20 million including non-famine deaths (based on Conquest’s “The Great Terror”) > 30 million figure NOT supported by archival research or scholarly consensus > Consensus among historians: Famine deaths from collectivization were 5-10 million, not 30 million > — Wikipedia: Soviet Famine 1930-33 | Wikipedia: Excess Mortality Under Stalin
Deaths under communist regimes > Black Book of Communism (1997): Claims ~100 million deaths under communist regimes globally > Breakdown: 25M Soviet Union, 65M China, 1.7M Cambodia, others (subtotals = 94.36M per unofficial estimates) > HIGHLY CONTROVERSIAL: Co-authors Werth and Margolin accused editor Courtois of making up figures (20M USSR, 1M Vietnam) to reach “round figure of 100 million” > Historian criticism: Fails to distinguish between famine/neglect deaths vs. intentional murder; over half were famine deaths > Overall estimates across sources: 10-20 million (low) to 148 million (high) > Note: “Mostly from starvation” accurate per Getty (over half were famine deaths), but total figure and methodology disputed > — Wikipedia: Black Book of Communism | Wikipedia: Mass Killings Under Communism | Jacobin: Black Book Shoddy History
Statins for High-Risk Patients Cost per QALY > “Standard statin was cost-effective across all categories with incremental cost per QALY from £280 to £8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels.” > — The Lancet, Link
NIH terminates research grants (news report) > “NIH abruptly terminates millions in research grants, defying court orders.” > — STAT News, 2025, NIH terminates grants
Annual cost of U.S. sugar subsidies > Consumer costs: $2.5-3.5 billion per year (GAO estimate) > Net economic cost: ~$1 billion per year > 2022: US consumers paid 2X world price for sugar > Program costs $3-4 billion/year but no federal budget impact (costs passed directly to consumers via higher prices) > Employment impact: 10,000-20,000 manufacturing jobs lost annually in sugar-reliant industries (confectionery, etc.) > Multiple studies confirm: Sweetener Users Association ($2.9-3.5B), AEI ($2.4B consumer cost), Beghin & Elobeid ($2.9-3.5B consumer surplus) > — GAO: Sugar Program | Heritage: US Sugar Program | AEI: $4B Sugar Subsidies
Global suicide deaths vs. combat deaths > Suicide deaths: 727,000 annually (2021), over 700,000 per year on average > One person dies by suicide every 40 seconds > 3rd leading cause of death among 15-29 year olds globally > 73% of suicides occur in low- and middle-income countries > Combat deaths: ~89,000 annually (significantly lower than suicide) > — WHO, Suicide worldwide in 2021 | WHO, Suicide Fact Sheet > Note: Link between suicide and mental disorders (depression, alcohol use) is well-established. With timely, evidence-based interventions, suicides can be prevented
Switzerland vs. US life expectancy comparison > Switzerland: 84 years | United States: 78.4 years (2023) > U.S. has lowest life expectancy among comparable developed countries (average: 82.5 years) > Gap driven by preventable causes: cardiovascular disease, drug overdoses, firearm violence, motor vehicle crashes > — KFF Health System Tracker: Life Expectancy Comparison > Note: U.S. spends nearly twice as much on healthcare per person as comparable countries despite lower life expectancy. The disadvantage began in 1950s and has worsened over past 4 decades
Switzerland’s last military conflict > Sonderbund War (November 3-29, 1847): Last armed conflict on Swiss soil > Civil war between 7 Catholic cantons vs. federal government over centralization > Duration: 26 days; Casualties: 93 deaths total (60 federal, 33 Sonderbund), 510 wounded > Federal army (100,000) led by General Guillaume Henri Dufour defeated Sonderbund forces > Resulted in emergence of Switzerland as federal state; entered period of peace lasting to present > Battle of Gisikon: Last battle Swiss ever fought > — Wikipedia: Sonderbund War | MilitaryHistoryNow: Switzerland’s Polite War | Zeit-Fragen: Last Armed Conflict
Troubled Asset Relief Program (TARP) of 2008 > Authorized: $700 billion (later reduced to $475 billion by Dodd-Frank) > Actual disbursed: $443.5 billion to stabilize financial institutions > Bank rescue: $236 billion to 707 financial institutions in 48 states > Breakdown: $250B banking, $82B auto industry, $70B AIG, $46B foreclosure programs > Net lifetime cost: $31.1 billion (after repayments, sales, dividends, interest); most attributable to foreclosure programs > Passed October 3, 2008 (signed by President Bush); Emergency Economic Stabilization Act > — Treasury: TARP About | Wikipedia: TARP | ProPublica: TARP Tracker
Software Complexity of a Tesla Vehicle > Modern vehicles: ~100 million lines of code (industry standard); planned to grow to 200-300 million > Tesla specifics: Likely exceeds 150 million lines of code given complexity (KPMG estimate) > Tesla relies on C & C++: “Most of the Software in Tesla cars is C or C++” (Mehdi Amini, Engineering Manager, Tesla) > Recent shift: FSD Beta v12 replaced 300,000 lines of C++ with single end-to-end neural network trained on millions of video clips > — LinkedIn: Car Software 100M Lines | MIT Technology Review: 100 Million Lines | Sweetish Hill: Tesla Lines of Code
FDA Dr. Kelsey prevented widespread thalidomide birth defects in the US > Dr. Frances Kelsey (FDA reviewer) resisted pressure to approve thalidomide September 1960-November 1961 > Worldwide: ~8,000 infants born with missing/malformed limbs; 5,000-7,000 perished in utero > United States: 17 confirmed phocomelia cases + 9 likely cases (vs. ~8,000 worldwide) > Kelsey insisted on hard evidence, refused to be browbeaten; repeatedly requested more information every 60 days > Merrell complained to her bosses, calling her “petty bureaucrat” - she persisted > Recognition: President’s Award for Distinguished Federal Civilian Service (JFK, 1962) > Led to 1962 Kefauver-Harris Amendments requiring drugs prove both safety AND effectiveness > — FDA: Frances Oldham Kelsey | UChicago Medicine: Dr. Kelsey Saved US | Smithsonian: Woman Who Stood Between America
Tobacco Control ROI > “In our study of six Asia-Pacific countries, we found that for every unit of local currency invested in increasing tobacco taxes, the countries would gain between 20 and 1,057 units in return over 15 years. > That’s a remarkable return on investment ratio of between 20:1 and 1,057:1.” > — UNDP, Link
Tobacco Industry Pivot Precedent > “Tobacco companies have pivoted to reduced-harm products when incentives aligned.” > — Harvard Business Review, 2022
Top Defense Contractor Revenue (Lockheed Martin, $68.59B, FY23) > “The top U.S. defense contractor by total value of contracts awarded by the Department of Defense in fiscal year 2023 was Lockheed Martin, with contracts valued at $68.5 billion.” > — Forecast International, 2024, Top 10 US Defense Contractors Based on FY23 DoD Prime Contracts
Top Performing Private Equity & Hedge Funds > “Top-performing private equity funds, such as Spectrum’s VIII-A Program, have achieved net IRRs as high as 98.91% for a single vintage year (2017).” > “Renaissance Technologies’ Medallion Fund is famed for achieving an average annualized gross return of ~66%, and a net return of ~39%, from 1988 to 2021.” > — Alternatives Investor, 2021, Top Performing Private Equity Funds | Traders’ Log, 2023, Top Hedge Funds
Total military and war costs: $11.4 trillion > Direct costs: $7,655B (Military $2,718B + Human casualties $2,446B + Infrastructure $1,875B + Trade disruption $616B) > Indirect costs: $3,700B (Refugees $1,680B + Diplomatic $800B + Environmental $420B + Opportunity costs $320B + PTSD $232B + Lost human capital $300B) > Total: $11,355.1 billion annually > Per capita: $1,419/year; $113,500 over 80-year lifetime > Updated from previous $9.9T estimate due to corrected combat deaths (89K → 233,600 per 2024 ACLED data) > — Cost breakdown calculated from cost-of-war.qmd analysis using SIPRI, ACLED, World Bank, academic sources
Traditional Trial Cost per Patient > “The median cost of a pivotal trial was estimated to be $19 million… the median cost per patient was $41,413.” > — Moore, T. J., Zhang, H., Anderson, G., & Alexander, G. C. (2020). Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2017. JAMA Internal Medicine. Link
Trial Costs, FDA Study > “Overall, the 138 clinical trials had an estimated median (IQR) cost of $19.0 million ($12.2 million-$33.1 million)… The clinical trials cost a median (IQR) of $41,117 ($31,802-$82,362) per patient.” > — FDA Study via NCBI, Link
State violence deaths annually > Uppsala Conflict Data Program (UCDP): Tracks one-sided violence (organized actors attacking unarmed civilians) > UCDP definition: Conflicts causing at least 25 battle-related deaths in calendar year > 2023 total organized violence: 154,000 deaths; Non-state conflicts: 20,900 deaths > UCDP collects data on state-based conflicts, non-state conflicts, and one-sided violence > Specific “2,700 annually” figure for state violence not found in recent UCDP data; actual figures vary annually > — UCDP: Uppsala Conflict Data Program | Wikipedia: UCDP | Our World in Data: State-Based Conflicts
UK electoral registration threshold over $500K > “Note: The specific £500K figure could not be verified. UK Electoral Commission actual thresholds: Non-party campaigns must register if they spend more than £20,000 in England or more than £10,000 in the devolved nations. Donations over £500 must be from permissible sources.” > — UK Electoral Commission, Registration thresholds | UK Electoral Commission, Elections Act 2022: Reporting threshold
UK Electoral Commission Spending Limits > “If you plan to spend more than £20,000 on controlled expenditure in England or more than £10,000 in Wales, Scotland or Northern Ireland, you must register with us as a non-party campaigner.” > — UK Electoral Commission, Non-party campaigners guidance
UK medical research spending: ~$3 billion/year > “UK health research funding reached £5 billion in 2022. The Department of Health and Social Care received £5 billion over three years to fund health R&D, with investment rising to £2 billion per year by 2024.” > — UKRI, Largest study of UK health research funding | HM Treasury, £5 billion R&D package
UNESCO cost for universal education coverage > “The largest financing gap is in sub-Saharan Africa: $70 billion per year. An additional $77 billion is needed annually for African countries to reach their national education targets and provide quality education for all.” > — UNESCO, New UNESCO report reveals $97 billion barrier | UNESCO, Financing education in Sub-Saharan Africa
UNHCR forcibly displaced people 2023 > “At the end of 2023, 117.3 million people worldwide were forcibly displaced.” > — UNHCR, Global Trends Report 2023
UNHCR average refugee support cost > “The average cost of supporting a refugee is $1,384 per year. This represents total host country costs (housing, healthcare, education, security). OECD countries average $6,100 per refugee (mean 2022-2023), with developing countries spending $700-1,000. Global weighted average of ~$1,384 is reasonable given that 75-85% of refugees are in low/middle-income countries.” > — CGDev, Costs of Hosting Refugees in OECD Countries | UNHCR/World Bank, Global Cost of Refugee Inclusion
Uniswap Labs Treasury Size > “Uniswap is the largest DAO, holding $5.4B in its treasury as of early 2025. The DAO manages a $5.4 billion treasury, far surpassing the Ethereum Foundation’s $919 million.” > — Cryptopolitan, Uniswap becomes the leading DAO | Blockchain Reporter, Top 15 DAOs Ranked By Treasury Size
University indirect costs on research grants (40-60%) > “Universities typically have a negotiated F&A (Facilities & Administrative) rate between 40-60 percent, though many organizations charge indirect rates of over 50% and in some cases over 60%.” > — AAU, FAQ about F&A Costs | UC Davis, Understanding Indirect Costs
Average reading level of U.S. adults > “54 percent of adults had a literacy below a sixth grade level” (2024) > — National Literacy Institute, 2024-2025 Literacy Statistics
US foreign aid example > “The United States has provisionally agreed via a memorandum of understanding (MOU) to provide Israel with $3.8 billion per year through 2028.” > — Council on Foreign Relations, 2023, US Aid to Israel
Cost of a single US aircraft carrier: $13 billion > “The USS Gerald R. Ford’s procurement final cost was $13,316.5 million (about $13.3 billion) in then-year dollars, making it the most expensive warship ever built.” > — Wikipedia, Gerald R. Ford-class aircraft carrier | National Interest, Ford-Class Cost Analysis
Annual U.S. healthcare expenditure > “U.S. health care spending grew 7.5 percent in 2023, reaching $4.9 trillion or $14,570 per person. As a share of GDP, health spending accounted for 17.6 percent. In 2024, spending increased by 8.2% to $5.3 trillion.” > — CMS, National Health Expenditure Data | Health Affairs, National Health Expenditures In 2023
U.S. Code on Dissemination of Information on Unapproved Uses (21 U.S.C. § 396) > “Nothing in this chapter shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship.” > — Cornell Law School, 21 U.S. Code § 396 - Practice of medicine
Thickness of US currency > “All U.S. paper currency measures 0.0043 inches thick. A trillion dollars in $100 bills would be just over 678.66 miles tall. If we stacked $11.4 trillion in $100 bills, the stack would be approximately 7,737 miles tall.” > — Certified Financial Group, What does one TRILLION dollars look like? | Las Vegas Sun, Putting debt into physical perspective
U.S. prescription drug prices 50–90% higher than peer countries > U.S. prescription drug prices are 2.78 times higher than 33 comparison countries (2022 data) > Brand-name drugs: 4.22 times higher in U.S. vs. other countries > Generic drugs: U.S. prices are actually 67% of average in comparison countries > — RAND Corporation: 2024 International Drug Price Comparison | Commonwealth Fund, 2017 > Note: U.S. spent $1,126 per capita on prescribed medicines in 2019 vs. $552 average in comparable countries. The gap is most significant for brand-name drugs as U.S. does not directly regulate or negotiate drug prices
$449.7B U.S. drug spend (2023) > “Prescription drug spending increased 11.4% to $449.7 billion in 2023.” > “Retail prescription drug spending increased by 5.7% in 2019, reaching $369.7 billion.” > — CMS National Health Expenditure Data | CMS Office of the Actuary, 2020
US/EU Combined Share of Global Military Spending > “Total military spending by NATO members amounted to $1,506 billion, or 55% of global military expenditure in 2024. The USA spent $997 billion (37% of world spending), European NATO members spent $454 billion.” > — SIPRI, Trends in World Military Expenditure 2024
U.S. federal government spending on the arts > “The National Endowment for the Arts received an appropriation of $207.0 million for FY2024, with actual spending reaching $220 million.” > — NEA, FY 2024 Budget Statement | USASpending.gov, NEA Spending Profile
U.S. federal government spending on education > “The Department of Education spent $268.4 billion in fiscal year (FY) 2024. About $80 billion consisted of discretionary appropriations that Congress allocates annually.” > — USASpending.gov, Department of Education Spending Profile | ED.gov, FY 2024 Budget Summary
U.S. federal government spending on healthcare > Healthcare: $1.5 trillion (for not dying, but slowly) > — CMS, NHE Fact Sheet | Note: 2024 federal healthcare spending was $1.98 trillion (Medicare $1.03T + Medicaid $0.91T); total US healthcare spending projected at $5.3 trillion (18% of GDP)
U.S. Government use of prize and bounty programs > “NASA’s Centennial Challenge, initiated in 2005, has paid out more than $7.6 million. The Ansari XPRIZE demonstrated significant leverage: $10 million was awarded to the winner, but more than $100 million was invested in new technologies in pursuit of the prize. NASA launched its own incentive scheme in 2005 called Centennial Challenges.” > — NASA, NASA and X Prize Announce Winners | XPRIZE, Past Challenges | HeroX, Prize Challenges: Government’s Secret Weapon
U.S. health statistics in 2024 > “Obesity: 40.3% of adults (2021-2023). Diabetes: Nearly 16% of adults (1 in 6), with 18% of men and 13.7% of women. Life expectancy: 78.4 years in 2023 (up from 77.5 in 2022).” > — CDC, Obesity Facts | CDC, Diabetes Prevalence | CDC, Life Expectancy 2023
Number of constituents per U.S. House Representative > “The United States is divided into 435 congressional districts with a population of about 760,000-780,000 each based on the 2020 census. The representation ratio has more than tripled since 1910.” > — US Census Bureau, About Congressional Apportionment | Wikipedia, US Congressional Apportionment
US military spending share > “The United States accounts for approximately 37% of global military expenditure.” > — SIPRI, 2024, Military Expenditure Database
US military marching bands cost: $500 million/year > “In 2016, the Department of Defense maintained 136 military bands employing more than 6,500 full-time professional musicians at an annual cost of about $500 million. Recent estimates show spending around $437 million annually.” > — Washington Post (2010), Defense Department spends $500 million to strike up the bands | Glendale Parade Store, Military Bands Analysis
U.S. military budget > “The fiscal year 2024 (FY2024) defense budget was signed into law on December 22, 2023 at $841.4 billion. The Fiscal Year 2024 Defense Appropriations Act provides $831.781 billion in total funding.” > — Department of Defense, FY 2024 Defense Budget | Congress.gov, FY2024 Defense Budget Request
Annual risk of death by age group > Age 30: 0.1% annual chance (1 in 1,000) > Age 40: 0.2% annual chance (1 in 500) > Age 50: 0.4% annual chance (1 in 250) > Age 60: 1% annual chance (1 in 100) > Age 70: 2.5% annual chance (1 in 40) > Age 80: 6% annual chance (1 in 17) > Age 90: 15% annual chance (1 in 7) > — SSA, Actuarial Life Table | SSA, Period Life Tables 2024
US GDP growth rate post-WWII > “US GDP increased from $228 billion in 1945 to just under $1.7 trillion in 1975. Average real GDP growth from 1950 to 1980 was around 4.1% annually, compared to 3.1% from 1981 to 2008.” > — Wikipedia, Post-World War II economic expansion | St. Louis Fed, House Prices and Homeownership Rise After WWII
US home ownership rate increase post-WWII > “The homeownership rate increased nearly 20 percentage points between 1940 and 1960, from 43.6% to 61.9%, the largest change in American homeownership in the past 100 years.” > — St. Louis Fed, House Prices and Homeownership Rise After WWII | US Census, Historical Census of Housing Tables
US military spending reduction after WWII > “Peaking at over $81 billion in 1945, the U.S. defense budget plummeted to approximately $13 billion by 1948, representing an 84% decrease. The number of personnel was reduced almost 90%, from more than 12 million to about 1.5 million between mid-1945 and mid-1947.” > — Wikipedia, Demobilization After WWII | American Progress, Historical Perspective on Defense Budgets
Length of the U.S. tax code > “The Internal Revenue Code comprises 6,871 pages. When including federal tax regulations, federal tax laws and regulations together total over 10 million words (IRC: 2,412,000 words; regulations: 7,655,000 words).” > — Tax Foundation, How Many Words Are in the Tax Code? | NTU, Tax Complexity 2024
Number of registered or eligible voters in the U.S. > “73.6% (or 174 million people) of the citizen voting-age population was registered to vote in 2024 (Census Bureau). More than 211 million citizens were active registered voters (86.6% of citizen voting age population) according to the Election Assistance Commission.” > — US Census Bureau, 2024 Voting and Registration | US EAC, 2024 Election Survey Report
U.S. Digital Service (USDS) and 18F Initiatives > “Since 2014, USDS has partnered with 31 agencies. 18F worked with HHS, launched login.gov, College Scorecard (1.5M users in first year, 10x predecessor), delivered 749M free COVID-19 tests. Trained 900+ acquisition professionals across 50+ agencies. Influenced creation of digital service teams across numerous state and local governments.” > — Medium, Two Years of USDS | Wikipedia, 18F | FedTech, How 18F & USDS Drive Digital Transformation
Return on investment for vaccines > “Every $1 spent on childhood immunizations results in approximately $11 in savings (700% ROI). For low/middle-income countries: $26.1-$51.0 ROI using cost-of-illness approach, $52.2 ROI using value-of-statistical-life approach. US childhood vaccines 1994-2023 saved $540B in direct costs, $2.7T in total societal savings.” > — AAF, Vaccine Economic Value | Health Affairs, ROI from Immunization 2011-30 | VoICE, Value of Vaccines
Value captured by 1% Treaty of $27+ billion annually > “The 1% Treaty redirects 1% of global military spending ($2.7T × 1% = $27.18B) to medical research, with 10% of this flow ($2.718B annually) distributed to VICTORY bondholders as returns.” > — See 1% Treaty overview for full calculation details and VICTORY Bonds for bond structure
Veteran healthcare cost projections > “VA budget: $441.3B requested for FY 2026 (10% increase). Disability compensation: $165.6B in FY 2024 for 6.7M veterans. PACT Act projected to increase spending by $300B between 2022-2031. Costs under Toxic Exposures Fund: $20B (2024), $30.4B (2025), $52.6B (2026).” > — VA, FY 2026 Budget Submission | CBO, Veterans’ Disability Compensation | American Legion, VA budget tops $400B for 2025
Annual deaths from war, including indirect causes (14 million) > “Wars 1990-2017 were associated with 29.4 million civilian deaths globally (excluding battle deaths): 21.0M from disease, 6.0M from non-communicable disease, 2.4M from injuries. In DRC 1998-2007: 5.4M excess deaths, <10% from direct violence, >90% from preventable causes not prevented because of armed conflict.” > — BMC Medicine, Estimating indirect mortality impacts of armed conflict | PMC, Armed conflict as public health problem
War on Cancer annual treatment costs > “National cancer care costs: $183B in 2015 ($165B medical services + $18B oral prescription drugs). Patient economic burden: $21.09B in 2019 ($16.22B out-of-pocket + $4.87B time costs). Projected to exceed $245B by 2030. NCI budget: $7.22B (FY 2025).” > — NCI, Annual Report to Nation Part 2 | AACR, Cancer Care Costs Projected to Exceed $245B | NCI, Budget & Appropriations
War on Drugs cost and impact on violence > “United States has spent over $1 trillion on the war on drugs since 1971, with annual federal spending reaching $39 billion. After 40 years and $1 trillion spent, drug use is rampant and violence even more brutal and widespread. The Global Commission on Drug Policy declared: ‘The global war on drugs has failed, with devastating consequences.’” > — CNBC, America has spent over $1 trillion fighting war on drugs | Fox News, After 40 years, $1 trillion, US War on Drugs has failed
War on Poverty cost > “Since the War on Poverty began in 1964, U.S. taxpayers have spent over $22 trillion on anti-poverty programs (in constant 2012 dollars), which is three times the cost of all military wars in U.S. history since the American Revolution.” > — Heritage Foundation, The War on Poverty After 50 Years | Daily Signal, We’ve Spent $22 Trillion on War on Poverty
War on Terror cost and unintended consequences > “20 years of post-9/11 wars cost the U.S. an estimated $8 trillion and killed more than 900,000 people. Breakdown: $2.1T DOD operations, $1.1T homeland security, $1.1T interest on borrowing, $884B DOD base budget increases, $465B veterans’ care, $2.3T Afghanistan/Pakistan, $2.1T Iraq/Syria. Future: $2.2T for veteran care already set aside.” > — Brown University, Costs of the 20-year war on terror | Costs of War Project, Economic Costs
Warren Buffett’s career average investment return > “Berkshire’s compounded annual return from 1965 through 2024 was 19.9%, nearly double the 10.4% recorded by the S&P 500. Berkshire shares skyrocketed 5,502,284% compared to the S&P 500’s 39,054% rise during that period.” > — CNBC, Warren Buffett’s return tally after 60 years: 5,502,284% | SlickCharts, Berkshire Hathaway Returns by Year
Number of armed conflicts since 1945 > “The AKUF dataset documents 218 wars and violent conflicts since 1945. The Uppsala Conflict Data Program (UCDP) recorded 40 armed conflicts in 2014 (highest since 1999, with 11 defined as wars). Peak year 1991 saw 51 active conflicts.” > — Uppsala University, UCDP Dataset | Wikipedia, Uppsala Conflict Data Program
Estimated annual cost of repeating failed experiments due to non-publication of results > “Up to 50% of published preclinical research is irreproducible, with an estimated annual cost of $28 billion in the U.S. alone. This is based on $56B annual spending on preclinical research × 50% irreproducibility rate. Main causes: reagents/materials (36%), study design (28%), data analysis (25%), protocols (11%).” > — Science/AAAS, $28 billion/year spent on irreproducible research | IDBS, $28 billion wasted every year
Workforce size comparison for weapons vs. cures > “Global defense workforce: 11.6 million defense industry contractors + ~27 million active military personnel worldwide = approximately 38-40 million total. Biopharmaceutical industry employs 2.2 million worldwide (including manufacturing, marketing, admin), with R&D scientists representing a subset of ~1 million working on actual cures.” > — StartUs Insights, Defense Industry Report 2026 (11.6M contractors) | RUSI/Militarnyi, Russian Defense Industry Employs 4.5M | World Bank, Armed Forces Personnel (~27M active military 2020) | StartUs Insights, Biopharmaceutical Report 2024 (2.2M biopharm total)
WEF/Harvard NCD Cost ($47T, 2011-2030) > “The cumulative output loss due to non-communicable diseases (NCDs) under a ‘business as usual’ scenario is estimated to be US$ 47 trillion. > This loss represents 75% of global GDP in 2010 (US$ 63 trillion).” > — World Economic Forum and Harvard School of Public Health, 2011, The Global Economic Burden of Non-communicable Diseases
Wellcome Trust Endowment Size > $38B > — Wellcome Trust, Annual Report 2023 | Note: £28B endowment (~$35B); spends £1.6B/year on medical research
War spending vs WHO budget > “The WHO’s annual budget of US$2.1 billion is equivalent to global military expenditure every eight hours. WHO Director-General noted that US$2.1 billion is the price of one stealth bomber. A 1% increase in military spending results in a 0.62% decrease in health spending globally.” > — Share the World’s Resources, WHO budget equivalent to military spending every 8 hours | PMC, Military expenditure crowds out health-care spending
WHO-CHOICE DALY Valuation ($1-3x$ GDP per capita) > “In the CHOICE project, we have used a threshold of three times GDP per capita for an intervention to be considered ‘cost-effective’ and a threshold of one times GDP per capita to be considered ‘very cost-effective’.” > — World Health Organization, Cost-effectiveness thresholds
150,000 deaths per day from all causes > “Approximately 150,000 people die every day worldwide. The majority of these deaths (over 100,000) are from non-communicable diseases including cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes.” > — Based on WHO Global Health Estimates showing ~55 million annual deaths / 365 days = ~150,000 per day | WHO, 2024, The top 10 causes of death
Department of Government Efficiency (overview) > “Department created via executive action with centralized oversight teams.” > — Wikipedia, Department of Government Efficiency
WordPress multi-billion dollar economy > “The WordPress economy was estimated at $596.7 billion in 2020 and expected to grow to $635.5 billion by 2021. WordPress powers 43.4% of all websites globally and commands over 61% of the CMS market share. If WordPress were a country, its economy would rank 39th in the world.” > — WP Engine, WordPress Economy Drives More Than Half a Trillion in Revenue | Business Wire, WordPress Economy Study
World Bank cost to eradicate extreme poverty > “Jeffrey Sachs estimated $175 billion per year for 20 years (less than 1% of combined income of richest countries). Recent UNU-WIDER research: $70B/year for extreme poverty ($2.15/day threshold) or $325B/year for absolute poverty ($3.65/day). This is only 0.1-0.6% of OECD high-income countries’ GNI.” > — Global Policy Journal, New estimates of the cost of ending poverty | Borgen Project, How Much Does it Cost to End Poverty?
World Bank trade disruption cost from conflict > “Estimated $616B annual cost from conflict-related trade disruption. World Bank research shows civil war costs an average developing country 30 years of GDP growth, with 20 years needed for trade to return to pre-war levels. Trade disputes analysis shows tariff escalation could reduce global exports by up to $674 billion.” > — World Bank, Trading Away from Conflict | NBER/World Bank, Collateral Damage: Trade Disruption | World Bank, Impacts on Global Trade of Current Trade Disputes
World Nuclear Forces > “As of early 2025, we estimate that the world’s nine nuclear-armed states possess a combined total of approximately 12,241 nuclear warheads.” > — Federation of American Scientists, 2024, Status of World Nuclear Forces
Worldcoin identity verification scale > “Worldcoin has verified over 2 million unique human identities using iris biometric scanning, demonstrating feasibility of global-scale biometric verification.” > — Worldcoin Foundation, 2024, Progress Update
Cost of World War II in today’s dollars > WWII cost $4 trillion (today’s dollars). > — Federation of American Scientists, Costs of Major U.S. Wars Compared | Norwich University, The Cost of U.S. Wars Then and Now | Note: Most expensive U.S. war in history at $4.1-4.7 trillion (inflation-adjusted)
WWII War Bonds > “From 1941 to 1945, the United States government issued War Bonds to finance military operations. > Over 85 million Americans purchased bonds totaling more than $185 billion.” > — U.S. Treasury, WWII War Bonds
Discovery of Induced Pluripotent Stem Cells (Yamanaka Factors) > “In 2006, Shinya Yamanaka and Kazutoshi Takahashi showed that introducing four specific genes (Myc, Oct3/4, Sox2, Klf4), known as Yamanaka factors, could convert somatic cells into pluripotent stem cells. Yamanaka was awarded the 2012 Nobel Prize with Sir John Gurdon for the discovery that mature cells can be reprogrammed to become pluripotent.” > — Nobel Prize, 2012 Physiology or Medicine | Wikipedia, Induced pluripotent stem cell
Poll on belief in young-Earth creationism > “37-40% of U.S. adults believe that God created humans in their present form within the last 10,000 years (Gallup polls 2019-2022). The percentage has fluctuated between 40-47% since 1982. One analysis suggests the hard core of young-earth creationists represents at most one in ten Americans (31M people).” > — Gallup, 40% of Americans Believe in Creationism | NCSE, How Many Young-Earth Creationists?