How Should We Do This Better Going Forward? A Biodistribution Transparency Framework for Next-Generation Medicine
Pattern recognition for institutional accountability when new platforms meet emergency decisions
OMFG. This make me doubt my very own existence, Well enough about my problems
Anyways here we go again.
“Don’t hate, Educate! This is not about what to think, it’s about how you could think!”
The question isn’t whether mRNA technology works. It does. The question is whether regulatory institutions communicated what they knew, when they knew it, in ways that preserved public trust for when we need this technology most.
Here’s what the documents show. Here’s what the pattern reveals. Here’s how we fix the process going forward.
Layer 1: What the Documents Actually Say
The European Medicines Agency’s February 2021 assessment report for Spikevax (Moderna’s mRNA COVID vaccine) contains biodistribution data from rat studies on page 47. The study used luciferase-tagged mRNA-LNP formulations and measured distribution across tissues.
What they found:
Measurable mRNA signal in injection site muscle (highest concentration)
Detectable levels in liver, spleen, bone marrow
Lower but measurable levels in heart, lung, kidney, brain tissue
Peak tissue levels within 24-48 hours, declining thereafter
What they documented:
Assay sensitivity limits (how low they could measure)
Species-specific considerations (rat metabolism ≠ human metabolism)
Dose scaling factors (rat dose adjusted for body surface area)
Route of administration (intramuscular injection)
This was animal data. These were preclinical studies. This information existed in regulatory files before conditional authorization was granted.
The gap: Public communication materials did not foreground these findings. Press releases emphasized “stays at injection site” messaging. Technical documents containing biodistribution data remained accessible but were not translated into lay-friendly summaries during the emergency authorization period.
Layer 2: Why Biodistribution Matters (The Mechanistic Primer)
Traditional vaccines work by showing your immune system a piece of the pathogen — like a wanted poster. Your body recognizes it, builds antibodies, and you’re protected.
mRNA vaccines work differently. They deliver genetic instructions that tell your own cells to temporarily manufacture the spike protein. Those cells then display the protein on their surface using a cellular mechanism called MHC Class I presentation.
Here’s the critical part: MHC Class I is the same system your immune system uses to identify virus-infected cells. When a cytotoxic T cell sees spike protein displayed this way, it does exactly what it’s trained to do — it kills that cell.
This mechanism is immunology 101. It’s not speculative. It’s textbook antigen presentation.
The question becomes: If LNP-delivered mRNA reaches cardiac tissue and those cells begin producing spike protein, what happens when cytotoxic T cells arrive?
Dr. Panagis Polykretis argued in a 2022 peer-reviewed paper (PMC9135042) that this mechanism creates a theoretical need for biodistribution evaluations before widespread deployment. His argument: if you’re turning cells into temporary antigen factories, you need to know which cells you’re converting and in what quantities.
This isn’t COVID-specific. It’s a property of systemic mRNA platforms. The same mechanism being used for personalized cancer vaccines (which is genuinely promising technology) creates the same theoretical concern about where those genetic instructions end up.
Layer 3: What Happened in Practice (The Epidemiological Reality)
Post-authorization surveillance detected a myocarditis signal concentrated in young males after dose 2. Multiple peer-reviewed studies documented this pattern:
Absolute rates (per million doses):
Males 12-17: approximately 50-70 cases per million second doses
Males 18-29: approximately 30-40 cases per million second doses
Females same age groups: 5-10 cases per million second doses
Clinical outcomes:
Most cases mild, resolving with supportive care
Some required hospitalization
Long-term outcomes still being monitored in registry studies
The mechanism linking mRNA biodistribution to myocarditis remains debated. Several hypotheses exist:
Direct cardiac uptake → local spike production → immune-mediated inflammation
Inflammatory cytokines from injection site affecting cardiac tissue
Individual variation in LNP pharmacokinetics
Age-related differences in immune response intensity
What’s established: Temporal association (timing aligned with vaccination), dose relationship (stronger after dose 2), demographic pattern (young males predominantly affected).
What’s not established: Direct causal proof would require tissue studies showing vaccine-generated spike in affected cardiac tissue + evidence of immune-mediated damage specifically to those cells.
The Institutional Pattern: Where Transparency Broke Down
This isn’t about assigning blame to individual scientists or regulators who made emergency decisions under unprecedented pressure. It’s about identifying systemic gaps so we don’t repeat them.
What didn’t happen:
Human biodistribution studies were not required before conditional authorization
Animal biodistribution findings were not prominently communicated to public audiences
Post-authorization surveillance plans for tissue-specific effects were not transparent
When signals emerged, the institutional response prioritized reassurance over mechanism investigation
The “They-ism” problem: When you ask “who decided human biodistribution data wasn’t needed?” the answer dissolves into committees, working groups, emergency protocols, and institutional processes. No individual is accountable. No document traces the decision logic.
This creates a democratic deficit. Citizens can’t evaluate whether appropriate tradeoffs were made if the decision architecture remains opaque.
How We Do This Better: A Forward-Looking Framework
These aren’t retroactive criticisms. They’re prospective requirements for next-generation platforms.
1. Biodistribution Transparency Standard
Require: Pre-authorization disclosure of all biodistribution data (animal or human) in public-facing summary documents, not just technical assessment reports.
Format: Two-page summary answering:
Which tissues showed measurable uptake?
What were the absolute concentrations?
How do animal findings translate to predicted human exposure?
What uncertainty remains?
Rationale: If regulators saw the data and judged it acceptable, the public deserves to see that same data and understand the reasoning.
2. Human Biodistribution Evidence Requirement
Default rule: For systemic-delivery gene platforms (mRNA, DNA, viral vector), human biodistribution data should be required unless regulators publicly document why it’s waived.
Methods could include:
Microdosing studies with imaging
Post-dose biopsy in surgical patients (opportunistic sampling)
Validated surrogate biomarkers correlated with tissue levels
Emergency exception: During genuine emergencies, conditional authorization can proceed with animal data PLUS a transparent post-authorization study commitment with published timelines.
3. Alarm Review Function
Create: Independent “Alarm Review” teams within regulatory agencies whose mandate is reviewing early safety signals and documenting decisions.
Requirements:
Publish monthly summaries of signals under investigation
Document why signals were pursued or dismissed (with evidence)
Make meeting minutes public with minimal redactions
Purpose: Replace “they-ism” with traceable accountability. If a signal was investigated and ruled unlikely causal, show the work. If a signal couldn’t be investigated due to resource limits, say so.
4. Stratified Communication
Acknowledge: Different populations face different risk-benefit ratios. Communication should reflect this.
Example: Young males with prior COVID infection face different myocarditis risk calculations than elderly immunocompromised individuals. Both groups deserve information calibrated to their situation.
Method: Risk communication should include:
Absolute numbers, not just relative risks
Age-stratified data
Comparison to baseline rates (e.g., myocarditis risk from COVID infection vs. vaccination)
Uncertainty bounds clearly stated
What This Is Not
This is not anti-vaccine advocacy. The evidence supporting vaccination’s population-level benefits during the COVID pandemic is overwhelming.
This is not a claim that mRNA vaccines “don’t work.” They demonstrably reduced severe disease and death.
This is not alleging conspiracy. Emergency decisions under uncertainty are genuinely difficult. Reasonable people can disagree about risk-benefit tradeoffs.
This is a call for institutional reform so the next time we deploy novel platforms at scale, we do so with transparency architecture that preserves public trust.
What Would Prove These Concerns Overblown?
Science advances through falsifiable claims. Here’s what would demonstrate that biodistribution concerns don’t translate to meaningful risk:
Human biodistribution studies showing tissue uptake levels orders of magnitude below concentrations capable of triggering immune responses
Mechanistic animal studies demonstrating dose thresholds exist and clinical doses fall well below them
Large-scale pathology studies (autopsy/biopsy) finding no correlation between vaccination and tissue inflammation in relevant organs
Long-term registry data showing adverse event rates return to baseline within months and produce no lasting sequelae
Some of this evidence exists. Some is still being gathered. The transparency gap isn’t about the existence of research — it’s about the accessibility of that research and the clarity of institutional communication.
The Pattern We’re Really Addressing
This same transparency architecture applies beyond mRNA vaccines:
Gene therapies using viral vectors face identical questions about tissue tropism and off-target effects.
CRISPR-based medicines will require biodistribution evidence showing genetic editing occurs where intended and nowhere else.
Personalized cancer vaccines (using the same mRNA-LNP platform) need transparent reporting of adverse events even as we celebrate their therapeutic potential.
The framework we build now determines whether publics will trust these technologies when we need them most. Every transparency failure is borrowed trust we’ll eventually have to repay — usually at the worst possible moment.
Start Where You Are: Practical Actions
If you’re a researcher:
Publish biodistribution data in openly accessible formats
Include lay summaries with technical papers
Participate in public communication efforts
If you’re a regulator:
Document decision logic in real-time, not retrospectively
Create public-facing dashboards for safety signal monitoring
Establish clear thresholds for when signals trigger investigation
If you’re a journalist:
Request specific documents (EMA assessment reports, FDA briefing materials)
Ask regulators to explain decision trees in plain language
Hold institutions accountable for transparency promises
If you’re a citizen:
Support organizations pushing for regulatory transparency
Demand that elected representatives codify these standards
Practice intellectual humility: uncertainty is honest, false certainty is dangerous
The Algorithm Still Works
Pay attention → Do your best → Pay it forward.
The institutions we have aren’t the institutions we need. That gap creates opportunity for systematic reform. The evidence exists. The policy frameworks exist. The political will must be generated.
This isn’t about relitigating 2021. It’s about building infrastructure for 2030, when the next novel platform reaches human populations at scale. We can be pro-innovation and pro-transparency simultaneously. The question is whether we have the collective will to demand both.
The documents are public. The mechanisms are knowable. The reforms are achievable.
What happens next depends on whether enough people decide transparency matters more than comfort.
Sources Referenced:
EMA Spikevax Assessment Report (Public domain, EMA website)
Polykretis et al. 2022, “Role of the antigen presentation process in mRNA vaccine biodistribution” (PMC9135042)
JAMA Network, “Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination” (2022)
Nature Reviews Cardiology, “Myocarditis after COVID-19 mRNA vaccination” (2021)
This article is public domain. Copy it. Improve it. Cite it. The goal is better governance, not content ownership.
🪶Peace, Love and Respect
David Foster Wallace wisely noted, “The most obvious important realities are often the ones that are hardest to see and talk about.” While seemingly a simple truth, in the daily struggles, such fundamental principles can be vital. Don’t mistake me for some sage dispensing profound wisdom. I’m not particularly wise, old, or even entirely convinced about the “soul” (mostly joking). This makes me relatable, one of us, not some distant authority.
This isn’t some obscure, ancient secret; it’s about us guiding each other in
“how to think”, not “what to think”.
Right? This is water.
I don’t know, Maybe i am wrong?
Tell me?
https://hejon07.substack.com/archive
This is excellent will share
One of the best, most lucid analyses of a topic talked about a lot but rarely understood I've seen. Thank you. And that throw-away line "The institutions we have aren’t the institutions we need" applies to so many.