If you are going to know it, then know it . . . Don't just know it.
It is one of my favorite sayings. Because the more I interact with someone online about vaccinations and viruses, the more I am understanding that most people know just enough to think they know everything but in reality, they really don't know anything about it.
I am usually the one that doesn't just barely know something, I will voraciously seek to know it inside and out. Because, I can't help myself, I am curious beyond reason.
So, here is a conversation I had with ChatGPT on viruses and vaccines. Because, if you want to know about vaccines, you might want to know as much as you can about virus's and immunity. This will take a long journey of probably hundreds of hour of video and reading. But - If I am going to know it, I am going to Know it . . . . not Just know it.
And before you judgmentally shut off because of ChatGPT - There are plenty of links and referenced books to support the discussion. I will be getting these and reading a bunch of them myself.
I would like to starting looking at how scientists know that viruses are real. I want to specifically look at how they get a sample, image them, and find their genetic sequence.
That's actually a very good place to start. If you want to evaluate claims about viruses—whether they're real, how they're detected, whether a particular virus causes a disease—you should begin with the basic methods scientists use.
A useful approach is to follow the same path a virologist would:
- Obtain a sample from a sick person
- Separate potential virus particles from everything else
- Grow or concentrate the virus
- Image the particles
- Extract genetic material
- Sequence the genome
- Compare it to other viral genomes
- Show that the virus can infect cells and reproduce
Let's walk through each step.
Step 1: Getting a Sample
Suppose doctors suspect a respiratory virus.
They might collect:
- Nasal swab
- Throat swab
- Lung fluid
- Blood sample
The sample contains a mixture of:
- Human cells
- Bacteria
- Mucus
- Proteins
- Dead material
- Possible virus particles
At this point nobody is looking at a "pure virus."
Step 2: Separating Virus Particles
Viruses are much smaller than cells.
Scientists use:
Filtration
Filters can remove:
- Human cells
- Most bacteria
while allowing tiny particles to pass through.
Centrifugation
Samples are spun at extremely high speeds.
Different materials separate according to size and density.
Viruses often form layers that can be collected.
A common technique is:
Density gradient centrifugation
where particles settle into layers inside a sugar solution.
This doesn't produce absolute purity, but it can enrich the sample greatly.
Step 3: Growing the Virus
Now scientists ask:
Can this material infect living cells?
They add the suspected virus-containing material to cultured cells.
Examples:
- Monkey kidney cells
- Human lung cells
- Vero cells
If a virus is present, the cells often show damage called a:
cytopathic effect
Examples:
- Cells round up
- Cells detach
- Cells fuse together
- Cells die
Scientists can then collect much larger amounts of virus from these infected cultures.
Step 4: Imaging the Virus
This is where many people first become skeptical.
Viruses are too small for ordinary light microscopes.
Scientists use:
Electron Microscopy
Electrons have much shorter wavelengths than visible light.
This allows imaging objects down to nanometer scales.
Typical virus sizes:
- Influenza ≈ 100 nm
- SARS-CoV-2 ≈ 80–120 nm
- Poliovirus ≈ 30 nm
Electron microscopy can directly show particles.
For example:
One important question you'll encounter is:
How do we know these aren't just random cellular debris?
Scientists don't rely on images alone.
The images are combined with:
- Genetic sequencing
- Infection experiments
- Repeated isolation
- Consistent particle structure
All of those lines of evidence point to the same object.
Step 5: Extracting Genetic Material
Viruses contain either:
- DNA
- RNA
Scientists chemically break open the particles and isolate the genetic material.
They can measure:
- Length
- Composition
- Structure
Different viruses have different genomes.
Examples:
| Virus | Genome Type |
|---|---|
| Herpes | DNA |
| Influenza | RNA |
| SARS-CoV-2 | RNA |
| Measles | RNA |
Step 6: Sequencing the Genome
This is where modern virology becomes extremely powerful.
Scientists determine the exact order of genetic letters.
Example:
AUGCUAGCGAAUCG...
for RNA
or
ATGCTAGCGAATCG...
for DNA.
Modern sequencing machines can read millions of fragments simultaneously.
Computers then assemble the genome.
This process is called:
Genome assembly
Step 7: Comparing Genomes
Once sequenced, scientists compare the genome with known viruses.
For example:
- Human SARS-CoV-2 genomes collected around the world are extraordinarily similar.
- Influenza strains show predictable mutation patterns.
- Measles viruses from different countries can be linked through their genetic relationships.
This is one reason scientists can build evolutionary trees for viruses.
If viruses were simply random debris, we would not expect to find reproducible genomes with consistent mutation patterns.
Step 8: Demonstrating Replication
The strongest evidence comes from showing that the particle:
- Enters cells
- Reproduces
- Produces more identical particles
- Produces identical genetic sequences
Scientists can observe:
- Viral proteins being made
- Viral RNA increasing
- New viral particles appearing
The virus essentially copies itself inside the host cell.
A Common Skeptical Question
One criticism you'll see is:
"Has a virus ever been truly isolated?"
The answer depends on what someone means by "isolated."
In chemistry, "isolated" often means completely pure.
In biology, especially virology, isolation generally means:
The virus has been separated, enriched, characterized, cultured, imaged, sequenced, and shown to replicate.
Virologists do not claim every preparation is 100% chemically pure. Instead, they use multiple independent methods that all point to the same biological entity.
If you want to dig deeper
I would suggest looking at these topics in order:
- What is electron microscopy and how does it work?
- Density-gradient centrifugation
- Cell culture and cytopathic effects
- How genome sequencing works
- How Koch's postulates were adapted for viruses
- How scientists isolated poliovirus, measles virus, and SARS-CoV-2
Poliovirus is especially useful because the evidence is older, simpler, and less politically charged than COVID-19. Following the history of how scientists isolated and studied poliovirus is one of the clearest ways to understand how virology established that viruses are real biological entities.
Are there any text books or videos you can give me that explains this?
Absolutely. If your goal is:
"How do scientists know viruses are real, and how do they isolate, image, and sequence them?"
then I would avoid starting with COVID-specific material. Start with general virology first. That gives you the tools to evaluate later claims for yourself.
Best Free Video Course
Vincent Racaniello's Columbia University Virology Lectures - an introduction
Vincent Racaniello is a virologist at Columbia University and co-author of one of the standard virology textbooks. His entire university virology course is available free online. The lectures start with basic questions like:
- What is a virus?
- How were viruses discovered?
- How are viruses isolated?
- How do they reproduce?
- How do scientists know they exist?
The lectures also have accompanying slides and study materials.
A particularly useful sequence would be:
- What is a Virus?
- The Infectious Cycle
- Genomes and Genetics
- Structure
- Attachment and Entry
These lectures directly address many of the questions virus skeptics raise.
Immunology course - an introduction -
Lecture 1 - https://youtu.be/JT0tUeyhLmY?si=v6JBgO_ICPVEXxgc
Lecture 2 - https://youtu.be/kJDcfB01FH0?si=zlhL89Dl42YHWJGM
Lecture 3 - https://youtu.be/CIS4C61sFa4?si=NK1UUUmk0_U9dxGV
Lecture 4 - https://youtu.be/9kLAKZc2uPY?si=5ncxsvnp1yLIvPsd
Lecture 5 - https://youtu.be/8DkM20EBYxg?si=dAbZ1pVo-8bcJ6tQ
Lecture 6 - https://youtu.be/8cpa1Qfu-cI?si=TbN1-O0GMi-ICcwr
Lecture 7 - https://youtu.be/Hklqulfk9Q8?si=B8mJ3hglR4a2NPSJ
Lecture 8 - https://youtu.be/uDvzc0VL9Bc?si=cuXfAOojYCn8RzBE
Lecture 9 - https://youtu.be/uDFWxtRQV-s?si=Nvk6YG0xFhO_ifOm
Lecture 10 - https://youtu.be/5yBtumgarZE?si=FwhY_a9PPkR-_E6h
Lecture 11 - https://youtu.be/S6ppwR6oeGA?si=ZLcvmBh60PHKZzLV
Lecture 12 - https://youtu.be/DcBzm82eXkE?si=gHlWn2MYoGqqLmqT
Lecture 13 - https://youtu.be/z-oTJOj9X6Y?si=xUfqJ2l4oV2lScu3
Lecture 14 - https://youtu.be/KA4C5GGSQ-E?si=qiBjzSUfORq6kYii
Lecture 15 - https://youtu.be/Dj8XXluyKXU?si=YbHdUhYm0IuxJxgI
Lecture 16 - https://youtu.be/9VEQZqeuvXM?si=zP6xDDomSv7U82tj
Lecture 17 - https://youtu.be/MLlSiQ7TGSI?si=HWGQuKBMWTAFPJUF
Lecture 18 - https://youtu.be/FALvwh6G2fo?si=Fne8Kh_Zx0yHXjn2
Lecture 19 - https://youtu.be/vBwEo_7br7g?si=P6cYrlKEhTdG66PH
Lecture 20 - https://youtu.be/HxSsUTXJQIo?si=cNMSiMstsyExGxBB
Lecture 21 - https://youtu.be/Y-8gXw5seCs?si=TZu5wbuIyHeg9AgV
Lecture 22 - https://youtu.be/xfsADiC5kDQ?si=tkr67kbYQVCe3ejS
Lecture 23 - https://youtu.be/_iT0WpMu6fk?si=keeY5OKQLEZR7I-g
Lecture 24 - https://youtu.be/q8A1_OclO14?si=1eLgsJIDue7ajgw6
Lecture 25 - https://youtu.be/IR3Vw-EbuuQ?si=o_UDSEEdwu1vu_zY
Best Textbook (University Level)
Principles of Virology
This is one of the most widely used university virology textbooks and is co-authored by Racaniello. It focuses on the common principles shared by all viruses rather than memorizing facts about individual diseases.
Principles of Virology (Wiley)
The chapters you would probably find most useful are:
- Virus Structure
- Viral Genomes
- Virus Replication
- Virus Isolation
- Virus Cultivation
- Electron Microscopy
Easier Textbook (Less Technical)
Cann's Principles of Molecular Virology
This is often recommended for people who want the science without jumping straight into graduate-level detail. It covers:
- Discovery of viruses
- Virus structure
- Electron microscopy
- Genome sequencing
- Virus replication
in a more approachable format.
Historical Case Study I Recommend
Instead of starting with SARS-CoV-2, start with:
Poliovirus
Why?
Because the evidence spans more than a century and isn't tied to current political debates.
You'll be able to examine:
- Isolation experiments
- Filtration experiments
- Cell culture
- Electron microscopy
- Genome sequencing
- Vaccine development
step by step.
If viruses aren't real, poliovirus becomes very difficult to explain because scientists repeatedly isolated it, grew it, photographed it, sequenced it, and used attenuated versions to create vaccines.
A Learning Path
If you want to investigate this as critically as possible, I'd suggest:
Week 1
- What is a virus?
- History of virology
- Why bacteria and viruses are different
Week 2
- Filtration
- Cell culture
- Viral isolation
Week 3
- Electron microscopy
- How virus images are produced
- Common criticisms of electron microscopy
Week 4
- DNA/RNA extraction
- Sequencing
- Genome assembly
Week 5
- Poliovirus case study
Week 6
- SARS-CoV-2 case study
By the time you reach COVID-related claims, you'll already understand the laboratory methods well enough to evaluate the arguments yourself.
One thing I can also do is walk you through an actual published virus isolation paper—showing every step from patient sample to electron micrograph to genome sequence. Poliovirus, measles, or SARS-CoV-2 would all work well for that.
Any other videos? Maybe geared towards high school level?
Yes. In fact, if you're approaching this as a curious adult rather than a biology major, I think high-school and introductory college resources are often better than university virology textbooks.
Here are the ones I'd put at the top of the list.
1. HHMI BioInteractive (My top recommendation)
HHMI makes resources specifically for high school and AP Biology students. Their virus materials include animations, 3D models, and explanations of how viruses are identified, classified, and studied.
A few particularly useful resources:
- Virus Explorer (interactive 3D virus models)
- Biology of SARS‑CoV‑2 (animations on infection, detection, evolution, and vaccination)
The "Detection" section is especially relevant because it explains how scientists detect viral RNA and identify infections.
2. Crash Course Biology – Viruses
Crash Course has a virus episode designed for a general audience. It covers:
- How viruses were discovered
- Why filtration experiments were important
- Viral structure
- DNA and RNA genomes
- How viruses infect cells
without assuming much prior biology knowledge.
Crash Course Biology: Viruses & Vaccines
3. "The Virus Hunter's Toolkit"
This is one I think you'd really enjoy because it focuses on how scientists know what they're looking at.
Topics include:
- Koch's postulates
- Plaque assays
- Identifying viruses by structure
- Using antibodies
- Classifying viruses by genome type
In other words, it focuses on the evidence-gathering process rather than just memorizing virus names.
4. Journey to the Microcosmos
If you're interested in microscopy in general, this YouTube channel is excellent. Most episodes are about bacteria, protists, and microscopic life rather than viruses, but it helps build intuition about how scientists observe things too small to see directly.
5. Veritasium – Scientific Discovery Style Videos
Not virus-specific, but Veritasium often covers:
- How scientists gather evidence
- Historical experiments
- How microscopy developed
- How genetics and sequencing work
These are useful for understanding the broader scientific methods behind virology.
If I were building a "viruses are real—show me the evidence" course
I'd do it in this order:
- Crash Course virus episode (big picture)
- HHMI Virus Explorer (what viruses look like)
- The Virus Hunter's Toolkit (how scientists identify viruses)
- Learn electron microscopy
- Learn genome sequencing
- Read a real virus isolation paper
That last step is where things get especially interesting. We can pull up an actual paper on poliovirus, measles, or SARS-CoV-2 and trace the evidence from:
- patient sample,
- to cell culture,
- to electron microscope image,
- to genome sequence.
That exercise tends to answer many of the questions people have about whether viruses are merely theoretical constructs or physically observed biological entities.
That's a logical next step. Once you understand how scientists identify and characterize a virus, the next question is:
"How do they use that information to make a vaccine?"
The answer depends on the type of vaccine.
The Big Picture
A vaccine is essentially a way to show your immune system a target before you encounter the actual disease.
To do that, scientists need to know things such as:
- What virus is causing the disease?
- What proteins are on its surface?
- What parts of the virus does the immune system recognize?
- How stable is the virus genetically?
That's where isolation, imaging, and sequencing become important.
Major Categories of Vaccines
1. Live Attenuated Vaccines
These contain a living virus that has been weakened.
Examples:
- Measles
- Mumps
- Rubella (MMR)
- Chickenpox (Varicella)
How they're made
Scientists isolate the virus and grow it repeatedly under unusual conditions.
Over time the virus accumulates mutations that make it less effective at infecting humans.
The weakened version is then used as a vaccine.
Advantages
- Often produces strong, long-lasting immunity.
- Sometimes only one or two doses are needed.
Disadvantages
- Not suitable for some immunocompromised people.
- More complex manufacturing.
2. Inactivated (Killed) Vaccines
These contain whole viruses that have been killed.
Examples:
- Original Salk polio vaccine
- Some influenza vaccines
- Rabies vaccines
How they're made
- Isolate virus.
- Grow large amounts.
- Chemically inactivate it so it cannot replicate.
The immune system still recognizes the viral structures.
Advantages
- Cannot reproduce in the body.
Disadvantages
- Often require boosters.
- May produce a weaker immune response than live vaccines.
3. Protein Subunit Vaccines
These contain only selected viral proteins.
Examples:
- Hepatitis B vaccine
- Novavax COVID vaccine
How they're made
Scientists determine which viral protein is most important for immune recognition.
For example:
- Hepatitis B surface antigen
- SARS-CoV-2 spike protein
That protein is manufactured and purified.
No whole virus is included.
Advantages
- Very targeted.
- No live virus.
Disadvantages
- Often require adjuvants and boosters.
4. Toxoid Vaccines
These are technically not viral vaccines.
They target bacterial toxins.
Examples:
- Tetanus
- Diphtheria
Scientists inactivate the toxin while preserving its shape.
The immune system learns to recognize the toxin.
5. Viral Vector Vaccines
Examples:
- Johnson & Johnson COVID vaccine
- AstraZeneca COVID vaccine
How they work
Scientists take a harmless virus (often an adenovirus).
They insert genetic instructions from another virus.
For COVID:
- Adenovirus carrier
- SARS-CoV-2 spike gene inserted
The carrier delivers the genetic instructions into cells.
Cells produce the target protein.
The immune system responds.
Why sequencing matters
You must know the genetic sequence of the target protein before you can insert it into the carrier virus.
6. mRNA Vaccines
Examples:
- Pfizer-BioNTech COVID vaccine
- Moderna COVID vaccine
How they work
Scientists sequence the virus.
They identify a target protein (for COVID, the spike protein).
They manufacture messenger RNA that contains instructions for making that protein.
The mRNA enters cells.
Cells temporarily produce the protein.
The immune system responds.
Why sequencing matters
This vaccine platform depends heavily on sequencing.
Once the viral genome is known, scientists can design an mRNA vaccine without growing huge quantities of virus.
How Detection and Sequencing Connect to Vaccines
Different vaccine types use viral information in different ways:
| Vaccine Type | Need Virus Isolation? | Need Sequencing? |
|---|---|---|
| Live attenuated | Yes | Helpful |
| Inactivated | Yes | Helpful |
| Protein subunit | Usually | Yes |
| Viral vector | Not necessarily after identification | Yes |
| mRNA | Not necessarily after identification | Yes |
A Historical Progression
Notice how vaccine technology changed over time:
Early vaccines
- Smallpox
- Rabies
- Polio
Scientists mostly relied on:
- Observation
- Culturing viruses
- Trial and error
Modern vaccines
Scientists use:
- Genome sequencing
- Protein structure analysis
- Computational biology
- Genetic engineering
Instead of asking:
"Can we weaken the virus?"
they increasingly ask:
"Which specific viral component produces protective immunity?"
A Useful Way to Think About It
You can divide vaccines into two broad groups:
Whole-virus vaccines
- Live attenuated
- Inactivated
These show the immune system most or all of the virus.
Component vaccines
- Protein subunit
- Viral vector
- mRNA
These show the immune system only selected pieces of the virus.
That distinction explains many of the discussions you'll see online about vaccine development, safety, immune response, and why different vaccines are made differently.
A good next step would be to take one disease—polio, measles, chickenpox, hepatitis B, or COVID-19—and trace exactly how scientists went from virus discovery → isolation → sequencing (if available) → vaccine development. That makes the connection between virology and vaccination very concrete.
Are there any lecture videos like the virus one above about the types of vaccines and how they work?
Yes, and since you liked Racaniello's virology lecture, I'd actually start with his vaccine lecture first because it builds directly on the virus concepts you've already begun exploring.
1. Vincent Racaniello – Vaccines (College Intro Level)
This lecture covers:
- Live attenuated vaccines
- Inactivated vaccines
- Subunit vaccines
- mRNA vaccines
- Viral vector vaccines
- Real examples using polio, influenza, hepatitis B, chickenpox, and HPV vaccines.
If you've already watched "What is a Virus?", this is probably the most natural next step.
2. TED-Ed: How Do Vaccines Work? (High School Level)
TED-Ed: How Do Vaccines Work?
This is only a few minutes long and is one of the clearest explanations I've seen.
It focuses on:
- Immune memory
- Why vaccines work before infection
- Historical origins of vaccination
- The basic concept without lots of jargon.
3. Harvard Medical School – Types of Vaccines
Harvard Medical School: Viruses and Vaccines
Harvard has a free animation series that includes a section specifically on:
- Traditional vaccines
- Modern vaccine technologies
- How different vaccine platforms stimulate immunity.
This is especially useful if you're trying to understand why an mRNA vaccine differs from a live-virus vaccine.
4. HHMI BioInteractive – Vaccination Animation
HHMI Vaccination Animation
HHMI designs materials for high-school and introductory college biology.
The animation walks through:
- What an antigen is
- How immune memory forms
- Different ways vaccines can deliver that antigen
- Why vaccination can occur without causing the disease itself.
5. CDC Explanation (Not a Lecture, but Excellent Background)
CDC: Explaining How Vaccines Work
This gives a straightforward overview of:
- Antigens
- Antibodies
- Immune memory
- Different vaccine approaches.
A Learning Sequence I'd Recommend
Since you're trying to connect virus detection → sequencing → vaccines, I'd watch them in this order:
- Racaniello: What Is a Virus?
- Racaniello: Vaccines
- TED-Ed: How Do Vaccines Work?
- HHMI Vaccination Animation
- Harvard Types of Vaccines
At that point you'll have enough background to understand questions like:
- Why did the polio vaccine use a whole virus?
- Why does the hepatitis B vaccine use only a protein?
- Why do mRNA vaccines require viral sequencing?
- What information from a virus genome is actually used to design a vaccine?
One topic that many people never get taught—but that ties everything together—is how scientists decide which part of a virus to target. For example, why the COVID vaccines focused on the spike protein rather than some other viral protein. That's where virology, sequencing, immunology, and vaccine design all intersect. We can dive into that next if you'd like.
Okay, let's talk a little history. Can you give me the story of how the first vaccines were developed and what problems they ran into that had to be solved. Include even mistakes and missteps and how vaccines and vaccine procedures changed after those.
Yes. And I think this is a really worthwhile way to study vaccine history, because the history isn't a story of scientists getting everything right from the beginning. It's much more interesting than that.
There were bad assumptions, dangerous experiments, manufacturing failures, unexpected side effects, ethical problems, and outright disasters. Importantly, many of those failures led to changes in how vaccines are tested, manufactured, monitored, and regulated.
I'd divide the history into a series of problems that scientists gradually learned how to solve.
1. Before vaccines: the first problem was simply surviving smallpox
Long before vaccination, people had discovered something rather strange:
If you deliberately gave someone a small amount of smallpox material, they were less likely to die from smallpox later.
This was called variolation.
The practice existed in various forms in Asia and Africa centuries before it became common in Europe. In China, for example, dried smallpox material was sometimes introduced through the nose. Other practices involved putting material from a smallpox lesion into a cut in the skin.
And this actually worked surprisingly well.
But there was a gigantic problem:
You were deliberately giving someone smallpox.
A person undergoing variolation could:
- become seriously ill
- die
- transmit smallpox to someone else
So the first vaccine problem was:
Can we get the protection without giving people the dangerous disease?
2. Jenner's solution: use a related but safer virus
In 1796, Edward Jenner tried something radically different.
He had observed that milkmaids who had experienced cowpox appeared to be protected from smallpox.
So Jenner took material from a cowpox lesion on a milkmaid, Sarah Nelmes, and inoculated an eight-year-old boy, James Phipps.
Phipps became mildly ill and recovered.
Then Jenner exposed him to smallpox.
He didn't develop smallpox.
Jenner repeated the experiment and published his findings.
This is the conceptual breakthrough:
You don't necessarily need to expose somebody to the disease-causing pathogen itself. A related organism can sometimes train the immune system to recognize it.
That is the basic idea behind many later vaccines.
3. But Jenner's vaccine wasn't remotely like today's vaccines
Here's something important when looking at historical vaccine claims:
The word "vaccine" has changed enormously in meaning.
Jenner didn't have:
- electron microscopes
- DNA sequencing
- cell culture
- molecular biology
- sterile manufacturing
- randomized controlled trials
- modern regulatory agencies
He didn't even know what a virus was in the modern sense.
He was working from observation and experimentation.
And early vaccine production was remarkably primitive by today's standards.
Smallpox vaccine was propagated through living biological material, and for a long time vaccine material was transferred arm-to-arm between people.
That created new problems.
4. Problem: contamination and consistency
If you're transferring biological material from one human being to another, you're not transferring only the thing you want.
You're potentially transferring other infectious agents too.
This became increasingly important as vaccination became industrialized.
The history of vaccination therefore moved toward:
"How do we make the same vaccine consistently, cleanly, and safely every time?"
That question eventually led to:
- controlled production
- sterile techniques
- standardized strains
- quality control
- testing of individual batches
- government inspection
But it took a long time to get there.
5. Pasteur changes the game
The next major revolution came with Louis Pasteur in the 1800s.
Pasteur demonstrated that microorganisms could be weakened and used to induce protection.
In 1879, his work with chicken cholera produced what WHO describes as the first laboratory-produced vaccine.
Then came his famous rabies work.
And this is a fascinating historical example because Pasteur was operating with enormous uncertainty.
6. The rabies vaccine: an ethically uncomfortable experiment
Rabies was essentially a death sentence once symptoms appeared.
Pasteur developed a method of weakening the infectious material and used it to treat people who had been bitten.
In 1885, nine-year-old Joseph Meister was bitten severely by a rabid dog.
Pasteur wasn't even a physician.
He decided that doing nothing would almost certainly mean death, while the experimental treatment might save him.
Meister received a series of increasingly potent preparations.
He survived.
But notice something important:
By modern standards, this wasn't an acceptable clinical trial.
There was:
- no modern Phase I/II/III system
- no randomized controlled trial
- no modern informed-consent framework
- no institutional review board
- no modern regulatory approval process
WHO explicitly notes that historical vaccine experiments included practices that would not be ethically acceptable today.
So vaccine science didn't simply advance because scientists were brilliant.
The ethical framework evolved too.
7. The next major breakthrough: understanding the actual pathogen
During the late 1800s and early 1900s, microbiology developed rapidly.
Scientists increasingly learned:
"There is a specific biological agent associated with a specific disease."
They developed:
- microscopy
- staining
- bacterial culture
- filtration
- animal models
- immunological techniques
But viruses presented an enormous problem.
They were too small to see with ordinary microscopes and couldn't initially be cultured like bacteria.
That brings us directly back to the question you started with:
How did scientists know viruses existed?
The answer developed gradually through experiments involving things like filtration and transmission before scientists could actually see individual virus particles.
8. Then came the polio problem
By the middle of the 20th century, scientists had learned enough about viruses to grow some of them in laboratory cells.
This was crucial.
Jonas Salk's inactivated polio vaccine depended on growing poliovirus, harvesting it, and then chemically inactivating it.
And that created a completely new engineering problem:
How do you kill every virus without destroying the structures necessary to produce immunity?
That sounds straightforward.
It wasn't.
9. The Cutter Incident — one of the biggest vaccine failures in history
This is one I definitely want you to study if you're interested in how vaccine procedures evolved.
In 1955, the first mass polio vaccination campaign began in the United States.
Millions of children were about to receive the vaccine.
But something went terribly wrong.
Some batches manufactured by Cutter Laboratories contained live poliovirus.
The virus hadn't been completely inactivated.
The vaccine that was supposed to prevent polio could actually cause polio.
More than 250 cases of polio were attributed to the affected vaccine, including paralysis and deaths.
The CDC's historical account describes the consequences as approximately 40,000 cases of paralytic polio detected in recently vaccinated children in the broader investigation, with 260 children paralyzed and 10 deaths in the early outbreak; epidemiologic investigation traced the problem to improperly produced vaccine batches.
This wasn't just a scientific failure.
It was a manufacturing and regulatory failure.
10. And this is where things get really interesting
The Cutter Incident forced a fundamental realization:
It isn't enough to prove that a vaccine works. You have to prove that every batch is manufactured correctly.
The government responded with much tighter manufacturing controls and oversight.
The vaccine program resumed after the processes were strengthened.
So you can see the evolution:
Early vaccination
"We found something that seems to work."
↓
Scientific vaccination
"Let's figure out why it works."
↓
Industrial vaccination
"Let's manufacture millions of doses."
↓
Modern vaccination
"Let's demonstrate efficacy AND control the manufacturing process AND monitor safety AND investigate unexpected adverse events."
That's a huge conceptual change.
11. Measles provides another beautiful example
Measles shows something that connects directly to your original interest in virus detection and sequencing.
In 1954, during a measles outbreak near Boston, researchers collected throat swabs and blood samples from infected children.
Thomas Peebles successfully isolated and cultivated measles virus from an 11-year-old boy, David Edmonston.
That virus became the Edmonston strain.
John Enders and colleagues subsequently developed the live attenuated measles vaccine from it.
This is almost exactly the pipeline you've been asking about:
Person with disease
→ sample
→ virus isolation
→ cultivation
→ characterization
→ attenuation
→ vaccine
→ clinical testing
→ licensed vaccine
That's a fantastic historical case study for us.
12. Another problem: vaccines aren't necessarily permanent
Scientists also discovered that immunity doesn't always last forever.
Some vaccines require:
- multiple doses
- boosters
- adjuvants
- different formulations
And sometimes the pathogen itself changes.
Influenza is the classic example.
The immune system recognizes specific molecular structures on the virus, but influenza viruses continually accumulate mutations.
So vaccine development becomes a moving target.
That eventually leads us toward:
genetic sequencing → surveillance → identifying circulating strains → updating vaccines.
And that's where your two subjects—virus detection and vaccine development—really merge.
13. Manufacturing problems kept teaching scientists lessons
Another example is the smallpox eradication campaign.
The original smallpox vaccine was effective, but it wasn't particularly convenient for a worldwide eradication program.
You needed something that could:
- survive transportation
- remain effective without perfect refrigeration
- be produced consistently
- be administered rapidly
- work in areas with limited medical infrastructure
Scientists developed freeze-dried vaccine, and the development of the bifurcated needle dramatically simplified administration and reduced the amount of vaccine needed.
Those weren't changes to the fundamental immunology.
They were engineering and logistical improvements.
And they mattered enormously.
14. The really important pattern
If we step back, vaccine history isn't simply:
"Scientists discovered vaccines and they worked."
It's more like this:
| Problem | What happened | What changed |
|---|---|---|
| Variolation caused disease | People intentionally received smallpox | Search for safer immunity |
| Jenner's early vaccine | Cowpox provided protection | Related-pathogen vaccination |
| Human-to-human vaccine propagation | Potential contamination/variability | More controlled production |
| Pasteur's experiments | Vaccines could be artificially developed | Laboratory vaccine development |
| Early human experimentation | Major ethical uncertainties | Modern research ethics gradually developed |
| Virus cultivation | Needed reliable virus production | Cell culture |
| Polio vaccine | Inactivation had to be reliable | Much stronger manufacturing controls |
| Cutter Incident | Live virus remained in vaccine | Regulatory/manufacturing oversight strengthened |
| Measles | Virus had to be isolated and cultivated | Virus isolation → attenuation → vaccine |
| Smallpox eradication | Vaccine needed to survive global distribution | Freeze-drying + improved delivery |
| Changing pathogens | Existing immunity may not match new strains | Surveillance + updated vaccines |
And that's the part I think you'll find most interesting.
Science didn't arrive at today's vaccine system in one giant leap.
It was more like:
Observation → hypothesis → experiment → failure → investigation → modification → better experiment → new failure → better safeguards.
That's actually one of the strongest arguments for looking at the history rather than simply being told "vaccines are safe."
You can ask:
What went wrong? How did they discover it? What did they change afterward? And does the modern system actually address the old failure?
That's a much more intellectually satisfying way to investigate this.
Where I'd go next
I'd suggest we take these one at a time, starting with Jenner and smallpox, and really dig into what he actually did—not the sanitized textbook version. Then we can move chronologically through Pasteur → rabies → diphtheria/tetanus → polio/Cutter → measles → recombinant vaccines → mRNA.
And for each one, we can keep the same four questions:
1. What did they know?
2. What did they not know?
3. What went wrong?
4. What changed because of it?
That will also give you a really good framework for understanding why modern vaccine testing and regulation look the way they do.
Could you give me videos or lectures on any of these stories?
Yes. I found several that fit exactly what you're doing, and I think we can build a pretty good little historical video curriculum out of them.
1. 🌟 Jenner & Smallpox — easiest starting point
Khan Academy — Eradicating Smallpox
Watch: Eradicating Smallpox
It's about 14 minutes and is aimed at an AP/high-school level. It starts with the history of smallpox and Edward Jenner, including the cowpox observation and James Phipps experiment, then follows the story all the way through eradication.
This would be my first one for you.
There's also a collection of historical vaccination videos from Dr. Jenner's House, including recorded lectures and discussions about smallpox eradication. Dr Jenner's House — Video Learning Resources
2. 🦠 Pasteur & the Rabies Vaccine
Patrick Kelly — The Origin of the Rabies Vaccine
This is a longer, story-driven video rather than a classroom lecture. It covers the biology of rabies, Pasteur's vaccine development, and the famous human cases that helped establish the vaccine. The creator also provides a source list and timestamps.
I think you'll particularly like this one because we can pause at each stage and ask "What did Pasteur actually know at this point?"
3. 🧬 Measles — this one is PERFECT for what you're studying
The measles story connects almost directly to your original question about virus detection → isolation → cultivation → vaccine.
In 1954, Enders and Thomas Peebles collected blood and throat samples during a measles outbreak near Boston and successfully isolated the virus from a sick child, David Edmonston. That strain eventually became the basis for the measles vaccine.
There's a particularly interesting PBS interview with David Edmonston himself:
PBS: The man whose blood helped develop the measles vaccine
He's the actual person whose sample helped lead to the vaccine.
That's a pretty remarkable historical connection to what you've been asking:
sick child → sample → virus isolation → cultivation → attenuation → vaccine
4. 💥 The Cutter Incident — ABSOLUTELY watch this one
This is probably the most important video for the part of your question about:
"What mistakes happened, and what changed because of them?"
The CDC has an entire recorded lecture:
"Conquering Polio in America: The Cutter Incident and Beyond."
CDC — Conquering Polio in America: The Cutter Incident and Beyond
This isn't a simplified "vaccines are good" presentation. It specifically examines the 1955 manufacturing failure, when some batches of inactivated polio vaccine contained live poliovirus. More than 250 cases of polio were attributed to Cutter's vaccine.
And importantly, it explains what happened afterward—how the incident changed vaccine manufacturing and government oversight.
That's exactly the type of history I think you're looking for.
5. One more measles resource
There's also a very good historical account from WHO:
WHO — History of Measles Vaccination
It isn't a video, but I'd keep it beside the PBS video because it gives you the actual chronology: isolation in 1954, early vaccine experiments, licensing in 1963, and the development of a less-reactive version by Maurice Hilleman in 1968.
The order I'd watch them
I'd actually make your "course" look like this:
1. Smallpox / Jenner
Khan Academy — Eradicating Smallpox
⬇️
2. Pasteur / Rabies
The Origin of the Rabies Vaccine
⬇️
3. Measles
PBS interview with David Edmonston
⬇️
4. Polio
CDC — Cutter Incident
⬇️
5. Then we go back to the laboratory
At that point I'd like to take one of those historical vaccines and reconstruct the actual laboratory process:
Where did the original biological material come from? → How was the pathogen isolated? → How did they know they'd actually isolated it? → How was it grown? → How was it weakened or killed? → How was the vaccine tested? → What went wrong? → What safeguards exist today because of those mistakes?
That last part is particularly important because it will let us connect your "How do we know viruses are real?" investigation directly to your "How did vaccines develop?" investigation, rather than treating them as two unrelated subjects.
Are there any educational movies that I could get a hold of about it?
Yes. And now that I know you're interested in the story of how the science developed—including failures and how those failures changed procedures—there are some much better choices than generic "how vaccines work" videos.
🎬 1. The Polio Crusade — PBS American Experience
This is probably the one I'd have you watch first. It's a full one-hour documentary about the race to develop the Salk polio vaccine.
It covers:
- The terrifying polio epidemics
- Jonas Salk
- Albert Sabin and their disagreement over vaccine strategy
- The enormous 1954 field trial involving nearly 2 million children
- The uncertainty surrounding the vaccine before the results were known
- The Cutter Incident
- The subsequent tightening of manufacturing oversight
- The eventual success of both Salk's and Sabin's vaccines
And importantly, it doesn't present the history as "scientists knew the answer and everyone else was wrong." It shows that scientists disagreed about the correct approach, and that there were genuine uncertainties.
This one fits your current investigation extremely well.
🎬 2. Shot Felt ’Round the World — PBS
Watch *Shot Felt ’Round the World*
This is another full-length (~67 minute) documentary about Salk and the polio vaccine.
What's particularly useful for you is that it goes into the scientific disagreement surrounding the vaccine. Salk was pursuing a killed/inactivated virus vaccine, while Sabin believed a weakened live virus was the better approach.
It also discusses previous failed attempts at polio vaccination and how those failures influenced Salk's approach.
I'd actually watch this after The Polio Crusade because they approach the story somewhat differently.
🎬 3. Rx for Survival: Disease Warriors — PBS/NOVA
PBS — *Rx for Survival: Disease Warriors*
This one is broader rather than focusing on one vaccine.
It covers the transition from a world where people didn't understand infectious disease to modern microbiology, including:
Pasteur → germs → rabies vaccine → smallpox → polio
That's useful because it puts vaccine development into the larger scientific story.
PBS describes it as following the groundbreaking work of researchers such as Louis Pasteur, including his development of the rabies vaccine, and then moving into smallpox eradication and the fight against polio.
🎬 4. A History of Vaccination — NOVA
Watch NOVA's *A History of Vaccination*
This is only about 5 minutes, so don't expect a deep dive.
But it gives you a nice historical overview starting with inoculation against smallpox and moving toward modern vaccination.
It's particularly good as an introduction before watching the longer documentaries.
🎬 5. Immunization: A History of Protection — PBS
Watch *Immunization: A History of Protection*
This is about 14 minutes and focuses specifically on how immunization changed public health.
It includes the development and introduction of the polio vaccine and interviews with a polio survivor.
And there's a really interesting Jenner one
🎬 From Cowpox to a Smallpox Vaccine — BBC
Watch *From Cowpox to a Smallpox Vaccine*
This is only 5:23, but it's specifically designed for grades 6–12.
It tells the Jenner story using historical reenactments and explains the transition from the dangerous practice of smallpox inoculation to Jenner's cowpox-based approach.
That's probably the best high-school-level historical introduction to the very beginning of vaccination.
If I were making this into a little "Vaccines: How We Got Here" movie course
I'd actually do:
1. 🐄 From Cowpox to a Smallpox Vaccine
2. 🦠 Rx for Survival: Disease Warriors
3. 🧪 The Polio Crusade
4. 💉 Shot Felt 'Round the World
5. Then go back and investigate the Cutter Incident specifically
The reason I particularly want you to see the Cutter material is that it gives you something that a lot of vaccine discussions leave out:
A vaccine can be scientifically effective and still have a catastrophic manufacturing failure.
And the response wasn't simply "trust the vaccine." The failure was investigated, the manufacturing problem was identified, and manufacturing standards and government oversight were changed. The PBS documentary explicitly discusses the lesson that the government needed substantially stronger oversight.
That's exactly the kind of historical evidence I think you're looking for: not just "vaccines work," but "here's what scientists thought, here's where they were wrong, here's how they discovered it, and here's what they changed afterward."
And there is actually a really fascinating next movie/documentary subject after polio: smallpox eradication itself—because that's where you get into vaccine production, vaccine quality, cold-chain problems, the bifurcated needle, surveillance, ring vaccination, and ultimately how scientists managed to eliminate an entire human disease.
Okay, now that we've worn ourselves out with looking at what viruses are how they're gathered how vaccines are made ... Let's look at this idea that people believe that viruses don't exist in that they never did. Where did that idea come from? Don't forget sources.
Yes. And there is an important distinction to make at the outset:
The idea that “viruses don't exist” is not the same thing as the historical scientific skepticism about germ theory. The modern claim is partly descended from older disagreements about what causes disease, but the specific assertion that viruses themselves are nonexistent is much newer.
I dug into the history, and there's a surprisingly traceable lineage.
1. The story starts before anyone even knew viruses existed
For most of human history, there were competing explanations for disease.
One was essentially miasma theory: disease came from poisonous or corrupted air, odors, environmental conditions, etc.
Another emerging idea was contagion: something was being transmitted from one person to another.
There were actually versions of germ theory going back centuries, but the modern experimental version developed in the 1800s through work by people including Pasteur and Koch. Historians emphasize that germ theory wasn't immediately accepted—it competed with several other explanations for disease.
So skepticism about infectious-disease theory is not new.
And that's important because some modern arguments essentially take a legitimate historical fact—
"Scientists once disagreed about what caused disease."
—and extend it into:
"Therefore the germ/virus explanation was never established."
Those aren't equivalent.
2. Enter Antoine Béchamp and "terrain theory"
This is one of the roots of the modern story.
French chemist Antoine Béchamp was a contemporary of Louis Pasteur. Béchamp emphasized the condition of the body's internal environment—the terrain—rather than treating microorganisms as the primary cause of disease.
The historical relationship between Béchamp and Pasteur is considerably more complicated than the internet version of:
"Béchamp was right and Pasteur stole his work."
Historians describe a much broader nineteenth-century debate involving germ theories, miasma, physiology, environmental conditions and the body's internal state.
And there's a subtle point here that is actually true and important:
The condition of the host really does matter.
Modern medicine absolutely recognizes that susceptibility to infection depends on things such as:
- immune status
- genetics
- age
- nutrition
- underlying disease
- previous immunity
- dose/exposure
- environment
A 1968 Lancet article even criticized an overly simplistic version of germ theory because infection depends on the interaction between germ, host and environment.
So:
"The body's condition matters" = legitimate science.
But:
"Therefore infectious viruses don't exist" = completely different claim.
3. Germ theory eventually won because it made testable predictions
This is where the history becomes really important.
Scientists didn't ultimately choose germ theory because Pasteur was more charismatic.
They began finding that microorganisms could be:
isolated → transferred → associated with disease → reproduced experimentally.
Robert Koch's work was particularly important in turning infectious disease into an experimentally testable field.
And then came something extraordinary:
Scientists began identifying specific organisms responsible for specific diseases.
But viruses created a new problem.
4. Viruses were initially mysterious
This is actually one of my favorite parts of the history because it connects directly to what we've been studying.
Scientists discovered that some infectious material could pass through filters that trapped bacteria.
The material was still infectious.
That meant:
Something smaller than known bacteria was capable of reproducing disease.
This happened before scientists could actually see individual viruses.
So early virology was built around experimental evidence of an unknown infectious agent, not pictures.
Then, over the following decades, scientists developed:
- filtration experiments
- animal transmission experiments
- cell culture
- ultracentrifugation
- electron microscopy
- biochemical characterization
- molecular biology
- genome sequencing
And the "invisible infectious agent" gradually became something that could be physically characterized.
Viruses were first recognized scientifically in the 1890s, decades after the major germ-theory debates.
5. So where does the modern "viruses don't exist" movement come from?
This is where things get much more recent.
One particularly influential figure is Stefan Lanka, a German biologist and longtime vaccine/HIV/AIDS skeptic.
In 2011, Lanka offered €100,000 to anyone who could provide scientific proof that the measles virus existed and determine its diameter.
A German physician, David Bardens, accepted the challenge and submitted six scientific papers.
The resulting legal battle is now routinely presented online as:
"German Supreme Court ruled that the measles virus doesn't exist."
That is false.
The court case was about whether Bardens had satisfied the specific conditions Lanka had written into his challenge.
A lower court initially ruled that Lanka owed the money.
On appeal, the court decided that Bardens hadn't fulfilled the literal requirement because Lanka had demanded one scientific publication, while Bardens submitted several papers whose evidence collectively established the case.
The appeal court did not conclude that measles virus doesn't exist. In fact, the expert evidence supported its existence. The German Federal Court of Justice subsequently declined to hear the further appeal.
This is one of the most important examples of how the modern claim spread.
6. And then something interesting happened to the story
The legal outcome became transformed online.
The original situation:
"Does this collection of papers satisfy the exact conditions of a €100,000 challenge?"
became:
"A German court couldn't prove measles exists."
Then:
"The German Supreme Court ruled measles doesn't exist."
And eventually:
"No scientific paper has ever proven viruses exist."
That's a completely different proposition.
Fact-checkers have documented this progression repeatedly.
7. COVID gave the idea a massive new audience
This is where the modern movement really exploded.
During COVID, people encountered arguments such as:
"They never isolated SARS-CoV-2."
"The genome was computer-generated."
"They never purified the virus."
"Electron microscope pictures are just cellular debris."
"The virus has never been proven to exist."
These arguments aren't all identical, but they share a common underlying challenge:
rejecting the experimental framework by which virologists identify viruses.
The COVID era also revived older "terrain theory" arguments.
A 2024 historical analysis in the University of Iowa's Poroi journal specifically traces modern viral denial back through Béchamp, terrain theory, and older germ-theory disputes, while noting that the modern movement substantially reshapes those historical ideas.
Popular Science similarly describes COVID as giving new life to the 160-year-old Pasteur/Béchamp conflict and to modern terrain theory communities.
8. There's an important distinction between three different positions
This is something I think will help us tremendously as we continue.
Position A — "Germ theory is too simplistic."
Reasonable scientific position.
Disease isn't determined by pathogen alone.
Host + pathogen + environment matter.
Position B — "Some historical experiments or modern virology methods deserve scrutiny."
Absolutely reasonable.
Scientists make mistakes.
Experiments can have:
- contamination
- controls that aren't adequate
- sampling problems
- statistical problems
- methodological limitations
- interpretation errors
That's normal science.
Position C — "Viruses have never been demonstrated to exist."
This is a radically different claim.
Because now you have to explain the enormous body of evidence from:
isolation → purification/enrichment → morphology → infectivity → replication → biochemical characterization → genetic sequencing → experimental manipulation → re-isolation.
And this is precisely why I think the groundwork we've been laying is useful.
We're not asking:
"Do I trust the CDC?"
We're asking:
"What physical experiment was performed, what did it actually show, and can we independently follow the chain of evidence?"
That's a much stronger question.
One thing I want to be careful about
I wouldn't tell you that every person who questions viruses got their ideas from Béchamp.
That's too simplistic.
The modern movement is a mixture of several traditions:
- historical anti-vaccination movements
- terrain theory
- alternative medicine
- distrust of pharmaceutical companies
- distrust of government
- HIV/AIDS denialism
- COVID-era skepticism
- misunderstandings about viral isolation
- misunderstanding of genome sequencing
- conspiracy theories
- legitimate criticism of particular scientific studies that gets generalized into rejection of virology
And some people arrive at the conclusion independently after encountering arguments about "purification" or "controls".
Those specific arguments deserve to be examined rather than simply dismissed.
And I think that's where we should go next
Now that we've traced where the idea comes from, I'd like to do something more rigorous than just fact-checking it.
Let's take the five or six strongest arguments made by modern virus-denial proponents and put each one through the same test:
What exactly are they claiming?
What experiment are they referring to?
Is their criticism scientifically legitimate?
What does the actual experiment show?
What would we expect to see if viruses didn't exist?
I'd start with "viruses have never actually been isolated/purified", because that's probably the single most important claim—and it directly connects to the sample → isolation → imaging → sequencing process we've already been learning about.
Okay let's start with that one then.
Yes. And you're right to call that out. If a previous answer was redacted, that was not a useful way to teach you the science, especially given that your goal is to examine the evidence critically rather than promote a harmful activity.
I can explain the limitation without reproducing whatever triggered the redaction.
What the concern was
The topic itself—"Have viruses actually been isolated?"—is completely legitimate and safe to discuss.
The problem can arise when an explanation gets too detailed about how to culture, propagate, concentrate, or experimentally manipulate infectious viruses. At a sufficiently operational level, that information can become a practical laboratory protocol for handling biological agents.
So there is a distinction between:
Safe and useful:
- What scientists mean by isolation
- What historical isolation experiments demonstrated
- Why filtration was important
- What electron microscopy contributes
- How sequencing provides independent evidence
- What controls were used
- What critics claim
- Whether those criticisms are scientifically valid
- Examining published experiments and their results
Potentially unsafe:
- Step-by-step instructions for propagating a particular infectious virus
- Exact culture conditions
- Specific quantities, concentrations, incubation conditions, or purification procedures
- Instructions for obtaining or producing infectious material
The first category is exactly what you're asking for. We don't need the second category to establish whether viruses exist.
And there's an important correction to the direction we were heading
We don't actually have to say:
"Trust scientists because they say they isolated a virus."
We can examine the evidence ourselves.
For example, with a historical virus, we can ask:
1. Was infectious material obtained from diseased animals or people?
2. Could it pass through a filter that removed bacteria?
3. Could the filtered material transmit the disease?
4. Could researchers repeatedly reproduce that observation?
5. Could the infectious agent subsequently be concentrated or separated from much of the surrounding biological material?
6. Could researchers observe particles with the expected size and morphology?
7. Could they extract nucleic acid associated with those particles?
8. Could they determine a reproducible genome sequence?
9. Could that sequence be detected independently in infected samples?
10. Could researchers experimentally alter or remove specific viral genes and observe predictable changes?
The really powerful point is that these are different kinds of evidence.
A virus isn't established merely because somebody took a picture of something through an electron microscope. And it isn't established merely because somebody found an RNA sequence.
The case becomes extraordinarily strong when physical, biological, biochemical, microscopic, and genetic observations converge on the same entity.
That's actually the investigation I think you wanted to do in the first place.
And we can absolutely do it without glossing over criticisms. If a virus-denial argument identifies a genuine weakness in an experiment, I'll tell you that. If the criticism depends on a misunderstanding of what "isolation" means, I'll explain that too.
If you'd like, let's now take the specific claim "SARS-CoV-2 was never isolated" and look at the original isolation papers—not somebody's summary of them—and examine exactly what researchers did and what evidence they obtained.
So you redacted it because someone could take that information and turn it into a bio weapon? That's the reason?
Yes—that's essentially the safety concern, with an important nuance.
The restriction isn't because information about viruses or virus isolation is inherently dangerous. It's because sufficiently operational instructions for culturing, concentrating, propagating, or modifying infectious biological agents could potentially be misused to cause harm.
So we can absolutely discuss:
- what "isolation" means scientifically;
- historical isolation experiments;
- what samples scientists used;
- what controls they used;
- microscopy and sequencing results;
- criticisms of those experiments;
- whether a particular paper actually supports its conclusions;
- and the historical evolution of laboratory methods.
What I shouldn't provide is a practical recipe for producing or manipulating an infectious virus—for example, precise experimental conditions that would turn the explanation into something someone could follow in a laboratory.
And importantly, we don't need those operational details to investigate whether viruses exist. We can examine the published evidence and reasoning in considerable depth without crossing that line.
Okay, let's get into the idea that people feel or have proof I guess that viruses cause more harm than they help. Specific claims like more deaths than the disease would give and worst side effects and those sort of things. Can you take the major points of that topic and comment to them?
Yes. And I think this is a good point to slow down and separate several claims that often get bundled together under “vaccines cause more harm than the disease.” Some versions of the argument contain a legitimate question; others rely on comparing completely different kinds of numbers.
The major claims I'd investigate are these:
1. “Vaccines have killed more people than the disease would have.”
This is a testable claim, but it requires a very particular comparison:
deaths actually caused by vaccination vs. deaths and serious illness that vaccination prevented.
A report that someone died after vaccination doesn't establish that the vaccine caused the death. That's especially important with VAERS and similar systems: they are designed to capture events occurring after vaccination, including events that turn out to be unrelated. CDC explicitly says this distinction is necessary, and vaccine-safety researchers investigate whether unusual patterns exceed what would normally be expected.
There are genuine vaccine-caused deaths in the historical record. They're not imaginary. For example, oral polio vaccine can very rarely cause vaccine-associated paralytic polio, and certain other vaccines have had exceptionally rare fatal complications.
So I would not phrase the question as:
“Have vaccines ever killed anyone?”
They have.
The meaningful question is:
How frequently does that happen, and how does that compare with the deaths prevented by the vaccine?
For routine vaccination, the available evidence overwhelmingly favors vaccination on that comparison. WHO estimates that immunization against 14 diseases alone saved at least 154 million lives over the past 50 years.
2. “The side effects are worse than the disease.”
Again, this needs to be broken down by which vaccine and which disease.
A sore arm and a fever aren't meaningfully comparable to encephalitis, paralysis, congenital rubella syndrome, cancer, or death.
But there are also legitimate rare vaccine injuries. For example, the rotavirus vaccine can very rarely cause intussusception. WHO and CDC don't pretend these risks don't exist; the question is whether the rare harm is outweighed by the disease prevented.
And this is an important principle:
A vaccine doesn't have to be risk-free to be beneficial.
It has to have a favorable risk-benefit ratio.
3. “If someone gets sick after vaccination, the vaccine caused it.”
This is probably one of the biggest sources of misleading statistics.
Imagine 10 million people are vaccinated.
Some of those people will subsequently:
- have heart attacks,
- develop cancer,
- get infections,
- have seizures,
- suffer accidents,
- die of unrelated causes.
Some of those events will happen the day after vaccination simply by coincidence.
That's why scientists distinguish:
Adverse event following vaccination
from
Adverse reaction caused by vaccination.
Those aren't synonymous. WHO specifically defines an adverse event following immunization as a medical problem occurring after vaccination that may or may not have been caused by the vaccine.
That's why raw VAERS numbers, for example, cannot legitimately be presented as “vaccines caused X deaths.”
4. “The government knew about all these deaths and hid them.”
This one is more complicated because there have been real vaccine safety failures and delayed recognition of problems.
That's actually part of the history we've already been studying.
The Cutter polio incident is an excellent example. Vaccine manufacturing failed, live poliovirus remained in some vaccine, people were harmed, investigators identified the problem, and manufacturing and regulatory procedures changed.
More recently, surveillance detected rare problems associated with COVID vaccines. For example, CDC says a causal association was established between the J&J/Janssen vaccine and thrombosis with thrombocytopenia syndrome; that finding contributed to recommendations favoring mRNA vaccines instead, and J&J is no longer available in the United States.
That's actually a pretty good demonstration of what a functioning safety system is supposed to do:
signal → investigation → causality assessment → change in recommendations.
It doesn't prove the system is perfect.
It does make the claim that “they never acknowledge vaccine injuries” demonstrably too broad.
5. “Vaccines cause chronic diseases that don't show up immediately.”
This is a more difficult claim scientifically because delayed effects are harder to detect.
That's precisely why vaccine safety surveillance doesn't stop when a vaccine is licensed.
Researchers continue looking for unexpected patterns among enormous populations.
And this is where large epidemiological studies become much more useful than individual anecdotes.
If a vaccine caused a chronic condition at a meaningful frequency, we'd expect something like:
vaccinated population → higher incidence of condition
unvaccinated population → lower incidence
with appropriate adjustment for differences between the groups.
If repeated studies fail to show that pattern, the causal hypothesis becomes increasingly difficult to sustain.
6. “Vaccines overload the immune system.”
This sounds intuitively plausible, but biologically it isn't a very good description of what vaccination does.
The immune system encounters enormous numbers of antigens every day. Vaccination exposes it to selected antigens so that it can develop immunological memory.
WHO describes the basic mechanism as the immune system recognizing an antigen, producing antibodies and developing memory that allows a faster response later.
So the interesting scientific question isn't:
“Does the immune system react to vaccines?”
It obviously does.
It's:
Does that immune activation produce more harm than the infection we're trying to prevent?
For most established vaccines against serious diseases, the evidence says no.
7. “The disease is actually safer than people were told.”
This one deserves serious investigation.
Disease severity isn't a single number.
For example, with measles, you could compare:
- infection fatality
- hospitalization
- pneumonia
- encephalitis
- long-term neurological complications
- SSPE
- complications in different age groups
versus:
- ordinary vaccine reactions
- serious vaccine reactions
- vaccine-associated complications.
You can do the same thing with:
polio vs. polio vaccine
chickenpox vs. varicella vaccine
hepatitis B vs. hepatitis B vaccine
HPV infection vs. HPV vaccination
etc.
That's much more informative than arguing about vaccines as one giant category.
And here's the really important point
I wouldn't start by asking:
“Are vaccines good or bad?”
I'd ask:
“For each vaccine, what benefit does it provide, what harms can it cause, how frequently do those harms occur, and how does that compare with the consequences of the disease?”
Because vaccines are not interchangeable.
A live attenuated vaccine, an mRNA vaccine, an inactivated vaccine and a protein-subunit vaccine have different mechanisms and different risk profiles.
And the disease matters enormously too.
The risk-benefit calculation for a vaccine against a potentially fatal disease isn't necessarily the same as for a vaccine against a generally mild disease.
One other thing I'd add to our investigation
We should not rely solely on CDC/WHO/FDA claims for this.
If we're going to really investigate the argument, I think we should deliberately use:
- randomized clinical trials
- large observational studies
- systematic reviews
- Cochrane reviews
- historical vaccine-safety investigations
- government surveillance data
- independent epidemiological research
For example, a Cochrane review of COVID-19 vaccines found substantial reductions in symptomatic COVID for several vaccines and large reductions in severe disease for several vaccines, while also noting where evidence about mortality or rare serious adverse events was insufficient. That's a much more nuanced picture than simply saying “vaccines are perfectly safe.”
That's the standard I'd like to use going forward: if the evidence is strong, we'll say it's strong; if it's weak or uncertain, we'll say that; and if there's a genuine vaccine injury signal, we won't explain it away just because it makes vaccines look bad.
The next really useful step would be to pick the claim “vaccines have caused more deaths than the diseases they prevent” and actually run the numbers for a few specific vaccines—starting with MMR, polio, and chickenpox. That would let us see exactly where these claims come from and whether the arithmetic survives scrutiny.
All right, but there has been times in history where vaccines have caused more harm than good, right?
Yes. There absolutely have been periods and specific situations where a vaccine caused more harm than benefit—either because the vaccine itself was defective, because the wrong population was vaccinated, or because the risks weren't understood yet. That's an important part of vaccine history, and acknowledging it doesn't undermine vaccination science.
The key is that these aren't all the same kind of failure.
1. Cutter polio vaccine — clear case of a vaccine causing harm
In 1955, some batches of Salk's inactivated polio vaccine contained live poliovirus because the inactivation process had failed. More than 250 cases of polio were attributed to Cutter vaccine, including paralysis and deaths. The CDC investigation traced the problem to particular batches and manufacturing practices.
This is an unambiguous example where:
The vaccine was supposed to prevent polio but actually caused polio.
And the response matters: manufacturing controls and government oversight were substantially strengthened afterward.
2. 1976 swine-flu vaccine — the risk-benefit calculation changed
In 1976, the U.S. vaccinated millions of people against a swine-origin influenza strain that officials feared could cause a major pandemic.
The feared pandemic didn't materialize, while surveillance detected an increased risk of Guillain-Barré syndrome (GBS) associated with the vaccine. CDC's historical assessment puts the excess risk at fewer than 10 GBS cases per million vaccinated people.
This is a different kind of failure:
The vaccine wasn't necessarily "bad" in the sense of being improperly manufactured. Rather, the disease threat turned out to be much smaller than anticipated, so the benefit side of the risk-benefit calculation collapsed.
That's a really important distinction.
3. Dengvaxia — perhaps the clearest modern example
The dengue vaccine Dengvaxia provides an especially interesting example because scientists eventually discovered that previous infection status mattered.
For people who had previously had dengue, the vaccine provided benefit.
But among people who had never previously been infected, subsequent evidence showed an increased risk of severe dengue and hospitalization. WHO consequently recommended that the vaccine not be given to people without previous dengue infection.
WHO estimated that among seronegative people, severe dengue occurred at roughly 4 per 1,000 vaccinated versus 1.7 per 1,000 unvaccinated over five years in the cited analysis.
That's a fascinating case because it demonstrates something important:
A vaccine can have a favorable benefit-risk profile in one population and an unfavorable one in another.
That's exactly why "Are vaccines safe?" is actually an incomplete question.
4. Contamination problems
There were also manufacturing problems that didn't necessarily produce immediate obvious disease.
For example, some polio vaccines produced from 1955–1963 were contaminated with SV40, a virus originating from monkey kidney cells used during manufacturing. CDC estimates that 10–30% of polio vaccines administered in the U.S. during that period contained SV40.
That sounds terrifying—and it absolutely deserved investigation.
But there's an important second half to the story: extensive subsequent research has not established that receiving SV40-contaminated polio vaccine caused cancer in humans.
That's a good example of why we shouldn't automatically turn:
"There was a contamination."
into:
"Therefore the contamination caused widespread disease."
Those are separate questions.
So your statement is correct—with an important qualification
If by:
"There have been times when vaccines caused more harm than good."
you mean specific vaccines, populations, periods, or batches, then yes.
The historical record supports that.
But if you mean:
"Vaccination as a whole has historically caused more deaths and disease than the diseases it prevents,"
that's a much stronger claim, and the evidence doesn't support it.
In fact, one of the fascinating things about the history is that the failures themselves helped create modern vaccine safety systems.
Cutter → stronger manufacturing controls.
SV40 → better testing for adventitious agents.
1976 GBS → improved post-licensure surveillance and risk-benefit assessment.
Dengvaxia → recognition that pre-existing immunity can change vaccine risk, leading to restrictions based on serostatus.
And that's exactly why I think your approach of looking at mistakes and corrections is better than simply asking whether vaccines are "safe."
We can now take this one step further and look at the really uncomfortable cases where the vaccine wasn't defective at all—it worked as designed, but scientists later discovered that its risk was higher than originally appreciated. Those are particularly useful for understanding how vaccine safety science actually works.
But those are not reasons to just stop using vaccines because those examples are just missteps in science discovery? Those are some pretty big misteps though because a lot of people suffered......
Exactly. “Those were missteps” doesn't mean they were small mistakes. Some were enormous failures with real victims. The important distinction is between “science sometimes makes catastrophic mistakes” and “therefore the scientific method can't tell us whether a vaccine is beneficial.”
The history actually gives us a pretty good example of why the distinction matters.
Cutter wasn't a minor error
The 1955 Cutter incident was a genuine public-health disaster. Some batches of inactivated polio vaccine contained live poliovirus. CDC's historical account says that 260 children were paralyzed and 10 died, and the investigation traced the problem to improperly produced vaccine.
And here's the part I think is especially important for what we're studying:
The vaccine had passed the required safety testing.
So the lesson wasn't simply "a scientist made a mistake." It exposed a weakness in the system used to manufacture and verify the product. The incident led to much more rigorous production controls and regulatory oversight.
That's a serious lesson.
The 1976 swine-flu episode is another good example
The government was responding to a plausible concern about a new influenza strain and vaccinated more than 40 million Americans. Surveillance then detected an excess of Guillain-Barré syndrome of about 1 additional case per 100,000 vaccinated people. Officials stopped the program while the association was investigated.
That's a fascinating example because the problem wasn't simply:
"The vaccine was manufactured incorrectly."
It was a risk-benefit judgment made under uncertainty.
The anticipated pandemic didn't materialize as feared, while an unexpected vaccine-associated risk emerged. Once the balance changed, the program was stopped.
That's actually what you would want a safety system to do.
So should these events make us stop using vaccines?
Not automatically.
But they absolutely should make us ask harder questions.
For any vaccine, I'd want to know:
1. What is the disease risk?
2. What are the known vaccine risks?
3. How confident are we about those numbers?
4. What serious adverse events were discovered during development?
5. What unexpected problems appeared after widespread use?
6. How good is the surveillance system at finding them?
7. What happens when a safety signal appears?
8. Has the vaccine's recommendation or manufacturing process changed as a result?
And crucially:
9. Does the benefit still outweigh the risk for the particular population we're talking about?
That's much better than asking whether vaccines are simply "safe" or "unsafe."
And I think your reaction to the historical mistakes is actually appropriate
I'd be suspicious of someone who told you:
"Don't worry about Cutter. Science makes mistakes."
No. People were harmed. It deserves to be taken seriously.
But I'd also be suspicious of someone who said:
"Cutter happened, therefore vaccines are inherently dangerous."
That doesn't follow either.
The scientifically interesting question is:
What failed, how was the failure detected, what was changed afterward, and does the modern system prevent that particular failure?
That's where the history becomes incredibly valuable.
For example, after Cutter, we don't merely have a story about children being injured. We have a natural experiment showing that surveillance detected an unexpected problem, epidemiologists identified the pattern, investigators distinguished the affected manufacturer's product from other vaccine products, the faulty product was withdrawn, and regulatory controls changed.
That's not evidence that the system is infallible.
It's evidence that the system can learn from failure.
And that's probably the central theme I'd use for the rest of our vaccine investigation:
We're not going to assume vaccines are safe because authorities say so. We're going to look at how the evidence for benefit and harm was actually established—and pay particular attention to the times scientists got it wrong.
That will give us a much more honest picture.
No I want to get on the topic of mRNA vaccines. How long has it been that they've been researching this type of medical intervention?
Yes—and this is one place where the phrase “mRNA vaccines were developed in record time” can be misleading if it gives the impression that scientists invented the underlying technology in 2020.
The COVID-19 mRNA vaccines were developed extraordinarily quickly, but the underlying science had been developing for roughly 30 years before COVID-19, with some of the foundational molecular biology going back to the 1960s.
A useful timeline
1961 — mRNA is discovered
Scientists identified messenger RNA as the intermediary that carries genetic information from DNA to the cellular machinery that makes proteins. That isn't vaccine research yet, but it's the fundamental biology on which the technology depends.
1970s–1980s — Scientists figure out how to work with RNA
Researchers learned how to isolate and manipulate mRNA and eventually how to synthesize it outside cells. By 1984, scientists had demonstrated laboratory synthesis of mRNA.
1989 — Major proof of concept
Researchers demonstrated that synthetic mRNA could be delivered into mammalian cells and that those cells would actually produce the protein encoded by the RNA.
That's a huge conceptual step:
Give a cell synthetic mRNA → cell reads it → cell makes the desired protein.
1990 — It works inside a living animal
Researchers injected mRNA into mouse muscle and demonstrated production of the encoded protein inside the animal. This is generally regarded as the first demonstration of mRNA's potential as an in-vivo gene-delivery technology.
1993 — First published mRNA vaccine
Researchers reported that synthetic, non-replicating mRNA could actually be used as a vaccine. They demonstrated an immune response to an mRNA-encoded antigen.
So by 1993, the basic concept of an mRNA vaccine already existed.
But there was a huge problem
The technology wasn't remotely ready for mass vaccination.
When researchers put synthetic mRNA into animals, the immune system could recognize the RNA itself and produce a strong inflammatory response.
And mRNA has another fundamental problem:
It's fragile.
It is naturally broken down relatively quickly, making it difficult to deliver enough of it to cells.
So for years the idea was essentially:
"This is incredibly interesting—but we don't yet know how to make it work well enough."
Those weren't trivial problems. They were major technological barriers.
2005 — the breakthrough
This is where Katalin Karikó and Drew Weissman become central.
They discovered that modifying one of the molecular building blocks of synthetic mRNA could dramatically reduce the undesirable innate immune response to the RNA while improving protein production.
Their key paper was published in 2005.
That discovery is what the 2023 Nobel Prize in Physiology or Medicine recognized.
And this is an important point:
Even after 2005, mRNA vaccines weren't suddenly ready for COVID.
There was still another decade-plus of work involving:
- delivery systems
- lipid nanoparticles
- RNA stability
- optimizing the RNA
- determining appropriate doses
- animal studies
- human clinical trials
- manufacturing
Researchers were already testing mRNA vaccines against diseases including rabies, influenza, Zika and cancer before COVID-19.
The first human clinical trials of mRNA vaccines began in the 2010s—a rabies vaccine trial in 2014 and an influenza vaccine trial in 2015.
Then COVID arrives
Here's the really remarkable part.
When SARS-CoV-2 emerged, scientists didn't have to invent mRNA vaccination from scratch.
They already had:
~60 years of basic mRNA biology
↓
~30 years of mRNA therapeutic/vaccine research
↓
~15 years of modified-mRNA research
↓
years of lipid-nanoparticle research
↓
animal studies
↓
early human trials
↓
then SARS-CoV-2's genome became available
And that last piece is where your earlier investigation into viral sequencing becomes really important.
Once researchers had the SARS-CoV-2 genome sequence, they could identify the sequence encoding the spike protein and design an mRNA vaccine around it. The first human mRNA COVID vaccine trial began enrolling in March 2020, and the first vaccines were being administered outside clinical trials by December 2020.
So the COVID vaccine development timeline was months, but the underlying technology's development timeline was decades.
And I think there's a fascinating question for us here
Given what we've been studying, I wouldn't stop at:
"How long have they been researching mRNA vaccines?"
I'd want to ask:
"What did researchers try along the way, what failed, and what problems had to be solved before mRNA became practical?"
Because there were some pretty spectacular failures and dead ends along the way.
For example, early mRNA research ran into problems with instability and excessive immune activation; researchers initially struggled to get funding; some scientists were skeptical that the technology would ever work; and the eventual successful approach required solving several independent problems rather than one magic discovery.
That makes mRNA a really good case study for the exact approach we've been taking with vaccines generally:
What did they know → what didn't work → what went wrong → what did they change → what evidence convinced them to proceed?
And we can trace that history from 1961 all the way to Pfizer/Moderna, including the failures and controversies rather than just telling the polished "Nobel Prize story."
So the technology was not experimental or new, it was just not an opportunity to put it to use, right?
Mostly yes, with an important distinction.
The underlying mRNA technology was not new in 2020, and it wasn't something scientists had suddenly invented for COVID. There had been decades of laboratory research, animal studies, and eventually human clinical trials involving mRNA vaccines before COVID-19.
But it would be inaccurate to say the technology was no longer experimental.
A better description is:
The scientific platform was well-established, but mRNA vaccination as a licensed human vaccine technology was still relatively new and had not yet been proven at the enormous scale of a worldwide vaccination program.
Before COVID:
- Synthetic mRNA had been demonstrated in cells in the 1980s.
- mRNA vaccines had been demonstrated experimentally by the 1990s.
- Modified mRNA substantially reduced some of the biggest problems in 2005.
- Lipid nanoparticles and other delivery technologies were developed over subsequent years.
- mRNA vaccines entered human clinical trials during the 2010s, including candidates for rabies and influenza.
- But no mRNA vaccine had yet been licensed for routine human use before COVID-19.
So when COVID appeared, scientists had something very unusual: a mature research platform that had never yet crossed the finish line into a licensed vaccine.
And that's why I would push back on both extremes:
“They invented an experimental technology in 2020.”
❌ Not accurate.
“The technology had already been completely proven and there was nothing experimental about it.”
❌ Also not accurate.
The more precise statement is:
COVID provided the opportunity—and enormous funding, urgency, and numbers of clinical cases—to take a technology that had been researched for decades through the final stages of human clinical development and regulatory approval.
And there's a really interesting distinction we should examine next: what exactly had already been demonstrated before 2020, versus what was still unknown when the first COVID mRNA vaccines were authorized.
That's where we can get past the slogans on both sides and see exactly how much was known and how much was genuinely uncertain.
Okay, so what are some disadvantages of mRNA vaccine technology?
Yes. And now that we've established that mRNA technology had decades of research behind it, we can look at its disadvantages without either exaggerating them or pretending they don't exist.
There are several, and they're worth separating into technology limitations and known health risks.
1. mRNA is inherently fragile
This is probably the biggest technological disadvantage.
RNA is chemically less stable than DNA. It is readily degraded, which creates problems with:
- storage
- transportation
- shelf life
- formulation
The lipid nanoparticles used to protect and deliver the mRNA also have stability issues. This was a significant problem for the original COVID vaccines and remains an active area of research.
That's why you historically saw the rather remarkable freezer requirements for some early COVID vaccines.
This is a genuine engineering disadvantage, not a safety conspiracy.
2. Getting the mRNA into the right cells is difficult
mRNA doesn't simply wander into cells and start working.
It's a large, negatively charged molecule and is rapidly degraded by enzymes in the body. Consequently, it needs a delivery system—most importantly, lipid nanoparticles (LNPs) in current vaccines.
That means you're really dealing with two technologies:
mRNA + delivery system
And the delivery system itself can affect:
- where the mRNA goes
- how much enters cells
- how long it remains active
- how strongly the immune system reacts
- tolerability
This is one reason researchers continue working on improved LNP formulations.
3. It can produce a fairly strong inflammatory reaction
This is somewhat paradoxical.
You want a vaccine to stimulate the immune system.
But you don't want unnecessary inflammation.
People commonly experience things like:
- sore arm
- fatigue
- headache
- fever
- muscle aches
- chills
after mRNA COVID vaccination. Most of these reactions are short-lived.
Scientists have spent considerable effort modifying mRNA so that it produces the desired immune response without excessive innate immune activation.
4. There is a real rare risk of myocarditis/pericarditis
This is one that should absolutely be included in an honest discussion.
Multiple surveillance systems have established a causal association between mRNA COVID vaccines and myocarditis/pericarditis. It occurs most frequently in adolescent and young adult males, particularly within about a week after the second dose.
And this isn't merely an old internet claim.
In June 2025, the FDA required updated warnings for Pfizer and Moderna's mRNA COVID vaccines. For the 2023–24 formulation, FDA estimated approximately:
- 8 cases per million doses overall among people 6 months–64 years
- 27 cases per million doses among males 12–24
during the 1–7 days after vaccination.
Most people with vaccine-associated myocarditis improve, but "rare" doesn't mean "irrelevant." FDA is continuing studies to determine whether there are longer-term cardiac consequences in people who experienced it.
That's an excellent example of the kind of thing we've been talking about throughout this conversation: a real adverse effect that was identified through surveillance and subsequently incorporated into the safety information.
5. Protection can decline relatively quickly
This is another legitimate limitation.
The first-generation COVID mRNA vaccines produced very strong protection against symptomatic infection initially, but protection against infection declined over time and as SARS-CoV-2 evolved.
More broadly, researchers have found that the durability of mRNA vaccine immunity can be less impressive than some long-lasting live vaccines, such as yellow fever vaccine.
That doesn't mean the vaccines "stopped working." It means we need to distinguish:
protection against infection
from
protection against severe disease.
Those aren't the same thing.
6. Multiple doses may be necessary
Related to the previous point, mRNA vaccination often works better as a prime/boost strategy rather than a single lifelong dose.
One of the ongoing goals of mRNA research is developing formulations that can produce longer-lasting protection and potentially work as one-shot vaccines.
That's a disadvantage compared with something like the yellow fever vaccine, where a single dose can provide extraordinarily durable protection for most people.
7. The lipid nanoparticles aren't biologically inert
This is an important point that sometimes gets lost in the phrase "it's just mRNA."
It isn't just mRNA.
The formulation contains lipid nanoparticles that protect the RNA and help deliver it into cells.
Those lipids can themselves interact with the immune system. Reviews have identified issues including inflammatory responses and, for some formulations, hypersensitivity reactions.
So when evaluating future mRNA vaccines, we shouldn't ask only:
"Is mRNA safe?"
We should ask:
"What mRNA, what modifications, what lipid nanoparticles, what dose, what route, and what population?"
Different formulations can have different properties.
8. We have less historical experience with the platform than with some older vaccine technologies
This is a more subtle disadvantage.
mRNA research itself goes back decades, but large-scale human use of mRNA vaccines began only with COVID-19.
That means the platform has accumulated much less real-world experience than vaccines such as:
- measles
- polio
- tetanus
- hepatitis B
- yellow fever
That doesn't mean we know nothing about mRNA vaccines. Billions of doses have provided an enormous amount of safety information.
But if you're asking:
"Do we have 50–70 years of population-level experience with mRNA vaccination?"
No.
That's a legitimate limitation.
One thing I would not put on the disadvantage list
You will sometimes hear:
"mRNA permanently alters your DNA."
That's not an established disadvantage of mRNA vaccines. The mRNA functions in the cytoplasm and is normally broken down; it does not need to enter the nucleus to produce the encoded protein.
That's different from saying nothing unexpected can ever happen biologically. But the specific claim that ordinary vaccine mRNA routinely integrates into human DNA isn't supported by the evidence.
So, if we put the disadvantages into categories
| Issue | Real concern? | What kind? |
|---|---|---|
| RNA instability | Yes | Technology/logistics |
| Difficult delivery | Yes | Technology |
| Strong short-term immune reactions | Yes | Reactogenicity |
| Myocarditis/pericarditis | Yes | Rare adverse effect |
| Waning protection | Yes | Effectiveness |
| Multiple doses/boosters | Yes | Practical limitation |
| LNP-related reactions | Yes | Formulation/safety |
| Less historical experience | Yes | Evidence/uncertainty |
| Permanent DNA alteration | No good evidence | Unsupported claim |
And I think there's an important connection to what we were discussing earlier:
None of these disadvantages automatically means "mRNA vaccines shouldn't exist."
They're things that have to be incorporated into the risk-benefit calculation for a particular vaccine, disease, age group, and formulation.
That's actually where I'd take our investigation next: the original Pfizer and Moderna trials versus what we learned after hundreds of millions/billions of doses. That's a really interesting way to see what the clinical trials successfully predicted, what they didn't predict, and what was discovered only after widespread use.
What are the limitations of mRNA technology?
Yes. If by “limitations of mRNA technology” you mean the technology itself—not just the side effects of a particular COVID vaccine—there are several important ones. Some have been substantially solved, while others remain active research problems.
1. mRNA is inherently unstable
RNA is chemically fragile and is readily degraded by enzymes called RNases. The molecule has to remain intact long enough to reach the appropriate cells and be translated into protein.
This creates practical problems with:
- shelf life
- storage
- transportation
- temperature sensitivity
- manufacturing consistency
This remains a significant limitation in 2026; researchers are still working on making mRNA vaccines more stable at ordinary refrigeration or room temperatures.
2. Getting mRNA into cells is difficult
mRNA is large and negatively charged, while the cell membrane presents a barrier to molecules with those properties.
Simply putting naked mRNA into the body doesn't work very efficiently. Much of it gets degraded or trapped before it reaches the cytoplasm, where it needs to be for protein production.
That's why modern mRNA vaccines use lipid nanoparticles (LNPs).
So the technology isn't really:
mRNA → injection → protein
It's more like:
mRNA → formulation → lipid nanoparticle → cell uptake → escape from the endosome → cytoplasm → protein production
Every step introduces another engineering problem.
3. The delivery system creates its own problems
The lipid nanoparticle isn't merely a passive container.
Researchers have to optimize its composition so that it:
- protects the RNA
- gets taken up by cells
- releases the RNA inside cells
- doesn't cause excessive toxicity or inflammation
- remains stable during storage
The Nature Reviews literature describes delivery as one of the major remaining challenges for mRNA technology.
This is particularly important because future mRNA medicines may need to deliver RNA to specific tissues, rather than simply producing an immune response.
4. The immune system can recognize the RNA itself
This is a fascinating problem.
The immune system has mechanisms for recognizing foreign RNA. Early synthetic mRNA therefore tended to trigger substantial innate immune responses, which could produce inflammation and simultaneously reduce the amount of protein the mRNA produced.
Scientists made enormous progress here through modified nucleosides and other RNA engineering.
But it illustrates something important:
The original concept of "just give the body mRNA" didn't work particularly well.
A considerable amount of engineering was required to make it practical.
5. You have to control how much protein is produced and for how long
The mRNA doesn't permanently change the cell's genetic instructions; it provides a temporary template for protein production.
But that means researchers need to optimize things such as:
- how much mRNA is delivered
- how efficiently cells translate it
- how long the RNA persists
- how much antigen is produced
Too little expression can produce inadequate immunity; too much can increase unwanted inflammatory responses.
This becomes even more complicated when you're trying to use mRNA for therapeutic purposes rather than vaccination.
6. Storage and distribution remain a weakness
This was particularly obvious with the first COVID vaccines.
The combination of fragile RNA and lipid nanoparticles created substantial temperature and stability requirements. Reviews continue to identify stability as one of the major barriers to widespread mRNA deployment.
This matters much more in:
- rural areas
- developing countries
- places with unreliable electricity
- mass vaccination campaigns
- situations where refrigeration is difficult
A vaccine that's scientifically excellent but difficult to keep stable isn't as useful as one that can sit safely in a normal refrigerator.
7. Manufacturing isn't as simple as the "rapid design" story makes it sound
One major advantage of mRNA is that once you know the sequence you want, the design can be changed very quickly.
But that doesn't mean you can instantly manufacture a perfect vaccine.
Manufacturers still have to control:
- RNA integrity
- purity
- the lipid components
- particle characteristics
- potency
- sterility
- consistency between batches
Manufacturing scale-up and quality control remain areas of research.
So there's an important distinction:
Design can be extremely fast.
Safe, consistent pharmaceutical manufacturing is not necessarily fast.
8. The immune response isn't necessarily long-lasting
This is more a limitation of some mRNA vaccine applications than an inherent property of every possible mRNA vaccine.
For COVID-19 specifically, protection against infection has waned over time, particularly as the virus evolved. This led to updated formulations and additional doses.
Researchers are therefore working on ways to produce:
- stronger mucosal immunity
- broader immunity against variants
- longer-lasting immune memory
- fewer doses
This isn't unique to mRNA, but it's an important challenge for the current technology.
9. The technology is still relatively young in actual human use
This is an important distinction from our previous conversation.
The science is decades old.
But large-scale human use is new.
We have enormous amounts of data from COVID vaccination now, but we don't have the same multi-generational experience with mRNA vaccines that we have with some older vaccine platforms.
That's not evidence that mRNA is unsafe. It's simply an evidence-history limitation.
So I'd divide the limitations into three categories
| Limitation | How serious is it? | Status |
|---|---|---|
| RNA degradation | Significant | Partially solved |
| Getting RNA into cells | Significant | Partially solved |
| LNP delivery | Significant | Active research |
| Unwanted immune activation | Significant | Substantially improved |
| Temperature stability | Significant | Active research |
| Manufacturing consistency | Significant | Active research |
| Duration of immunity | Depends on application | Active research |
| Tissue-specific delivery | Very important for therapeutics | Major research challenge |
| Long-term human experience | Limited compared with older platforms | Improving rapidly |
And there's a really interesting distinction here:
mRNA's biggest limitations aren't necessarily "mRNA is dangerous."
Many of its biggest limitations are engineering problems:
Keep it intact → get it to the right cell → get it into the cytoplasm → make the right amount of protein → avoid unnecessary inflammation → keep the product stable → manufacture it consistently.
Scientists have solved enough of those problems to make the technology work at enormous scale, but they haven't solved all of them. That's why mRNA research is still very active.
And this actually gives us a nice next question for your investigation: what did the original COVID mRNA vaccine trials know about these limitations in 2020, and what did scientists only discover after hundreds of millions of people received the vaccines? That's where the distinction between known limitations and unexpected safety findings becomes really useful.
There's a lot being said about mRNA vaccines changing DNA or hiding out in different organs of the body for long periods of time. Is any of that true? And what's the evidence for it?
This is a good question because there are actually two separate claims that often get lumped together:
- "The vaccine changes your DNA."
- "The vaccine or its products travel around the body and persist longer than originally advertised."
The evidence for these claims is very different.
Claim 1: "mRNA vaccines change your DNA"
What would have to happen?
For ordinary vaccine mRNA to become part of your DNA, several things would need to occur:
- The mRNA would need to enter cells.
- It would need to be converted into DNA by an enzyme called reverse transcriptase.
- That DNA would need to enter the nucleus.
- It would need to integrate into a chromosome.
Scientists agree that the vaccine mRNA does enter cells—that's the whole point of the technology.
The controversy is about the later steps.
What does the evidence show?
The strongest evidence we have is that:
- Vaccine mRNA functions in the cytoplasm, not the nucleus.
- It is degraded over time.
- Regulators and molecular biologists have not found evidence that routine vaccination causes genomic integration in people.
There have been laboratory studies showing that under artificial conditions, RNA can sometimes be reverse-transcribed in cultured cells. But that's very different from demonstrating:
"Vaccinated people are having vaccine sequences inserted into their chromosomes."
That latter claim has not been established by the evidence currently available. Regulators and multiple reviews continue to conclude that there is no credible evidence that mRNA COVID vaccines routinely alter human DNA.
What about the DNA contamination argument?
A newer version of the claim is:
"The problem isn't the mRNA—it's residual DNA from manufacturing."
There really are tiny amounts of residual plasmid DNA left over from the manufacturing process. The question is whether those amounts are dangerous.
Recent studies using validated methods found residual DNA levels below regulatory limits, and regulators state they have not seen evidence linking these trace amounts to genetic changes or health problems.
So the honest summary is:
The concern exists and has been investigated.
The claim that mRNA vaccines have been shown to alter human DNA has not been demonstrated.
Claim 2: "The vaccine stays in the body for a long time"
This one is more interesting because there's actually a kernel of truth mixed with oversimplification.
Early public messaging
Many people came away with the impression that:
"The vaccine stays in your arm and disappears in a day or two."
That turns out to be an oversimplification.
Animal and human studies show that:
- Most vaccine material remains near the injection site and lymphatic tissues.
- Some vaccine components can be detected elsewhere in the body.
- Small amounts have been found in tissues beyond the injection site.
So if someone claims:
"The vaccine does not remain exclusively in the arm."
That is true.
Does it reach other organs?
Studies have detected vaccine-related material or lipid nanoparticles in:
- lymph nodes
- spleen
- liver
and at much lower levels in some other tissues in animal studies.
The important question is not:
"Can it be detected?"
Almost anything injected into the body will distribute to some extent.
The important question is:
How much reaches those tissues, for how long, and does it cause harm?
That's where the debate shifts from simple detection to biological significance.
How long does it persist?
This is where things become more nuanced.
The original expectation was that mRNA would be cleared relatively quickly.
Many studies do show rapid decline over days to weeks.
However, later studies detected vaccine-related mRNA or vaccine-produced proteins longer than initially expected in some tissues, particularly lymphoid tissues involved in immune responses. Some studies found detectable vaccine-related material weeks or even months later.
That does not automatically mean harm.
Detection and injury are not the same thing.
But it is fair to say:
The simplistic statement that all vaccine-related material disappears everywhere in the body within a few days is not supported by all of the later research.
So where does that leave us?
If I were grading the claims:
"mRNA vaccines change your DNA."
Current evidence: Not supported. No convincing evidence has shown routine genomic integration in vaccinated people.
"The vaccine never leaves the arm."
Current evidence: False. Distribution beyond the injection site has been documented.
"The vaccine stays somewhere in the body longer than originally suggested."
Current evidence: Partly true. Some studies have detected vaccine-related mRNA or protein for longer periods than many people were initially led to believe, especially in lymphoid tissues.
"Long-term persistence proves the vaccines are harmful."
Current evidence: Not established. Detecting material is not the same thing as demonstrating disease or injury. That requires a separate line of evidence.
One thing I think is worth emphasizing is that this topic often gets polarized into two extremes:
- "It vanishes immediately and goes nowhere."
- "It spreads everywhere and permanently alters your body."
The actual scientific literature is much less dramatic. It shows some distribution beyond the injection site, mostly transient persistence, ongoing research into how long various components remain detectable, and no convincing evidence that the vaccines routinely alter human DNA.
Isn't there mechanisms in the cell to take care of foreign DNA? Foreign DNA can't just change your DNA. There's backups in protections in place for that isn't there?
Yes. In fact, that's one of the reasons many molecular biologists were never very persuaded by the simplistic claim that:
"A little bit of foreign DNA got into a cell, therefore it changed your genome."
Cells are not passive bags of chemicals. They have multiple layers of defense against foreign genetic material.
Some of the major ones are:
1. Foreign DNA is detected as a danger signal
Cells contain sensors that detect DNA in places where DNA normally shouldn't be, particularly in the cytoplasm. When foreign or misplaced DNA is detected, cells can trigger antiviral and inflammatory responses through pathways such as cGAS-STING.
In other words:
DNA floating around in the wrong compartment is often treated as suspicious.
2. Cells actively degrade foreign DNA
Humans have enzymes whose job is to destroy unwanted DNA.
For example:
- DNases break down DNA.
- TREX1 helps clear abnormal DNA from the cytoplasm.
- APOBEC proteins can chemically damage foreign DNA and promote its destruction.
One review even describes vertebrates as having evolved sophisticated systems to detect, restrict, and eliminate foreign nucleic acids.
3. The nucleus is physically separated
Your chromosomes are inside the nucleus.
Getting DNA into a cell is one challenge.
Getting it into the nucleus is another challenge.
Getting it incorporated into a chromosome is yet another challenge.
The cell doesn't simply take every DNA fragment it encounters and paste it into its genome.
4. DNA repair systems constantly patrol the genome
Cells continuously monitor DNA for breaks and abnormalities.
These DNA damage response systems:
- detect DNA damage,
- repair many forms of damage,
- trigger cell death if damage is severe,
- coordinate with immune pathways.
That's one reason cancers don't occur every time a DNA molecule is damaged.
Your cells are constantly repairing DNA.
5. Integration is usually a rare event
There are situations where foreign genetic material can become part of a genome:
- retroviruses such as HIV use specialized enzymes for this purpose,
- some gene-therapy vectors are designed to integrate,
- random integration can occasionally occur under certain circumstances.
But these are notable precisely because integration is not the default outcome.
Many viruses have evolved elaborate mechanisms specifically because host cells resist foreign genetic material so effectively.
A useful analogy
Imagine your genome as a secure library.
For foreign DNA to become part of the collection, it isn't enough to toss a book through the front door.
The book would need to:
- Survive security.
- Get into the archive room.
- Find the correct shelf.
- Be inserted into the catalog.
- Avoid being removed by librarians.
Cells have multiple "security guards" and "librarians" performing those functions.
Does that mean integration is impossible?
No.
Biology is full of exceptions.
If you ask:
"Can foreign genetic material ever become incorporated into cellular DNA?"
The answer is yes, it can happen under some circumstances.
If you ask:
"Does the mere presence of foreign DNA automatically mean your DNA has been changed?"
The answer is no.
That's where many public discussions go wrong. They skip over all the barriers and assume:
foreign DNA present → genome changed
when the real situation is:
foreign DNA present → multiple detection, degradation, repair, and compartmentalization systems act against that outcome.
And that's why, when scientists evaluate claims about vaccines altering DNA, they don't just ask:
"Was DNA present?"
They ask:
"Can you show actual integration into chromosomes in living humans, at meaningful levels, and demonstrate that it produces biological effects?"
That's a much higher evidentiary bar than simply detecting a fragment of DNA somewhere in a cell.
In the lecture you gave me a link to, the instructor said that up to 8% of our DNA comes from viral origins. Is there any other sources you can give about that?
Yes. The lecturer is referring to a well-established area of genetics called human endogenous retroviruses (HERVs).
The "about 8% of our DNA is viral in origin" statement is not coming from one obscure paper. It's found in textbooks, review articles, NIH materials, and genome research literature.
What exactly does "8% viral DNA" mean?
It does not mean:
- 8% of your DNA is active virus.
- 8% of your cells are infected.
- You are 8% virus in the everyday sense.
It means that during evolution, some retroviruses infected the germ cells (sperm- or egg-producing cells) of our ancestors. Because those infections occurred in cells that contribute to offspring, the viral DNA became part of the inherited genome and was passed down generation after generation. Over millions of years, those viral sequences accumulated mutations and became genetic fossils.
Good sources
NIH
The NIH explains that nearly one-tenth of the human genome contains DNA left behind by ancient viral infections and that some of these sequences may even contribute useful functions today.
Human Genome Research
A classic paper published shortly after the Human Genome Project reported that roughly 8% of the human genome consists of sequences recognizable as retroviral in origin.
Modern Review Article
A 2023 review in Physiological Genomics states:
"Approximately 8% of the human genome comprises sequences of viral origin."
It then explains how these elements arose from ancient retroviral infections of our ancestors' germ cells.
What's especially interesting
The story gets even stranger.
Scientists used to think these sequences were mostly useless "junk DNA."
Now we know some viral genes were apparently co-opted by evolution and put to work for us.
One famous example is a protein called syncytin.
Syncytin is derived from an ancient retroviral envelope gene and is important in the formation of the placenta. In other words:
A gene that originally came from a virus appears to have become part of normal mammalian reproduction.
This is one of the reasons biologists find endogenous retroviruses so fascinating.
Does this mean viruses can insert DNA into genomes?
For retroviruses, yes—that is literally part of their life cycle.
Retroviruses (such as HIV) carry RNA, convert it to DNA using reverse transcriptase, and then integrate that DNA into the host genome. That's why ancient retroviral fossils are found in our chromosomes in the first place.
But this is also where an important distinction comes in:
- Ancient retroviral integration over evolutionary time is a documented phenomenon.
- An mRNA vaccine routinely integrating into human DNA is a completely different claim that would require separate evidence.
People sometimes jump from the first statement to the second, but they are not the same thing.
If you're interested in the strongest evidence
One of the most compelling pieces isn't just that humans have these sequences.
It's that closely related primates often have the same endogenous retroviruses inserted at the same chromosomal locations.
Scientists can compare humans, chimpanzees, gorillas, and other primates and find matching viral insertions inherited from common ancestors. That is one reason endogenous retroviruses became an important line of evidence in evolutionary biology.
So the lecturer's "8%" figure is not fringe at all. It's actually a mainstream finding from genome research that has been repeatedly confirmed for more than two decades.
And it leads to a fascinating question that ties directly into our earlier discussion:
If our genomes contain millions of years of viral fossils, how do scientists distinguish between ancient viral DNA that became part of us and new foreign genetic material that enters a cell today?
That's where all those DNA-defense and DNA-repair mechanisms we were talking about become especially important.
Ok, so the real question is whether or not the mRNA vaccines can have the chance of becoming part of our genome. If it is possible that parts of retroviruses can change our DNA then it is also possible for the mRNA that is in vaccines could also, right?
You're asking exactly the right question, and the answer is a little more nuanced than either side of the debate usually presents.
The answer is:
Yes, in principle it is possible for RNA-derived sequences to become part of a genome.
But "possible in principle" is not the same thing as "shown to occur in vaccinated people at a meaningful rate."
Those are two different questions.
What we know from biology
We know that:
- Retroviruses can integrate genetic material into genomes.
- Human cells contain LINE-1 (L1) retrotransposons, which have reverse-transcriptase activity.
- Throughout evolution, RNA-derived sequences have occasionally become incorporated into genomes.
- Endogenous retroviruses are evidence that such events have happened in our ancestors.
So if someone says:
"It is biologically impossible for RNA-derived material ever to become DNA and integrate into a genome,"
that's too strong.
Biology has already shown us examples where RNA-derived sequences ended up in genomes.
The real question
The real question is:
Does vaccine mRNA do this in actual vaccinated humans?
And that's where the evidence changes.
Scientists have proposed theoretical pathways involving LINE-1 machinery that could, in principle, reverse-transcribe vaccine RNA. Some researchers have argued that this possibility deserves investigation rather than dismissal.
However:
- No study has demonstrated genomic integration of vaccine mRNA in vaccine recipients.
- The often-cited Lund University study used a liver cancer cell line under artificial laboratory conditions and did not show integration into the genome of vaccinated humans.
- Reviews from WHO, EMA, and multiple scientific reviews conclude that the risk is considered negligible based on what is currently known about cell biology and the behavior of vaccine mRNA.
Why many molecular biologists aren't very worried
Think about what has to happen:
- Vaccine mRNA must enter a cell.
- It must avoid degradation.
- Reverse transcriptase must be present and active.
- The RNA must be copied into DNA.
- That DNA must get into the nucleus.
- The DNA must become integrated into a chromosome.
- The cell must survive and reproduce.
- The event must occur often enough to matter biologically.
Each step is possible in isolation.
The question is the probability of the entire chain occurring in ordinary human cells. Reviews of the field generally conclude that the combined probability is extremely low.
An analogy
Suppose I ask:
"Is it possible for a meteorite to land in my backyard?"
Yes.
It has happened to people.
But that doesn't tell us how likely it is for your backyard this year.
Likewise:
"Can RNA-derived sequences ever end up in genomes?"
Yes.
That is established biology.
But that fact alone does not demonstrate:
"The Pfizer or Moderna vaccine changes the DNA of vaccinated people."
That requires direct evidence.
Where the evidence stands today
If I were summarizing the state of the science as fairly as possible:
Supported:
- RNA-derived sequences can become genomic DNA under some circumstances.
- Human cells contain machinery that can, at least theoretically, participate in such processes.
- Ancient viral sequences in our genome prove that genome integration events have occurred during evolution.
Plausible but unproven:
- Vaccine mRNA could theoretically be reverse-transcribed under rare circumstances.
- Some scientists have argued that the possibility should continue to be studied.
Not demonstrated:
- Routine integration of vaccine mRNA into the genomes of vaccinated humans.
- Clinically significant DNA alteration caused by mRNA vaccination.
- Population-level health effects resulting from such integration.
So the strongest scientifically defensible position right now is neither:
"Absolutely impossible."
nor
"It definitely changes people's DNA."
It's:
"There are theoretical mechanisms by which RNA-derived sequences can become part of genomes, but despite extensive use of mRNA vaccines, researchers have not demonstrated that this occurs in vaccinated people at a biologically meaningful level."
That's the distinction most public discussions skip over. They often jump directly from possibility to proof, when those are very different standards of evidence.
Ok, now onto viruses jumping species. Give me a text book like "class" of the concept of infectious viruses jumping from one species to another.
Great topic. The formal term is usually "zoonotic spillover" or "cross-species transmission." This is one of the central concepts in modern virology, epidemiology, and infectious disease biology.
A textbook-style class on the subject would typically cover:
Lesson 1: What is species jumping?
A species jump occurs when a pathogen that normally infects one species acquires the ability to infect another species.
Examples:
- HIV originated from simian immunodeficiency viruses in primates.
- Influenza viruses frequently move between birds, pigs, and humans.
- SARS-CoV emerged from animal reservoirs before infecting humans.
- MERS-CoV is associated with camels as an intermediate host.
- Rabies can infect many mammalian species.
The key idea is:
Most pathogens are adapted to a particular host species.
A species jump occurs when the pathogen overcomes those host-specific barriers.
Lesson 2: Why don't viruses infect everything?
A common misconception is:
"If viruses are everywhere, why aren't we constantly infected by animal viruses?"
Because infection is actually quite difficult.
Viruses must:
- Reach a host.
- Enter host cells.
- Replicate inside those cells.
- Evade immune defenses.
- Exit and spread to new hosts.
Failure at any step stops the infection.
Lesson 3: The receptor problem
This is usually the first barrier discussed in virology courses.
Viruses typically attach to specific molecules on cell surfaces called receptors.
Think of a receptor as a lock and the viral attachment protein as a key.
If the key doesn't fit:
- no entry
- no infection
For example:
- Human influenza viruses preferentially bind one form of sialic acid receptor.
- Bird influenza viruses preferentially bind a different form.
This receptor mismatch is one reason most bird flu viruses do not efficiently infect humans.
Lesson 4: Entry isn't enough
Suppose a virus gets inside a cell.
It still faces many problems.
The virus must hijack:
- cellular machinery
- protein synthesis
- replication pathways
Different species have different cellular environments.
A virus that replicates beautifully in a bat cell may replicate poorly in a human cell.
Lesson 5: Immune defenses
Even if a virus enters and replicates:
the immune system may stop it.
Different species have:
- different interferon responses
- different innate immunity
- different adaptive immunity
Many species jumps fail because the immune system suppresses the virus before sustained transmission occurs.
Lesson 6: Mutation
This is where evolution enters the picture.
Viruses mutate.
Especially:
- RNA viruses
- influenza
- coronaviruses
- HIV
Every replication cycle creates opportunities for genetic changes.
Most mutations are:
- neutral
- harmful to the virus
A few improve fitness.
Occasionally a mutation improves the virus's ability to infect a new host.
Lesson 7: Recombination and reassortment
Viruses don't always evolve one mutation at a time.
Sometimes they exchange genetic material.
Recombination
Common in coronaviruses.
Pieces of genomes can be swapped.
Reassortment
Occurs in influenza.
If two influenza strains infect the same cell:
- genome segments can mix
- entirely new combinations emerge
This is one reason influenza is watched so carefully.
Lesson 8: Spillover versus establishment
Many viruses infect humans occasionally.
Very few become established.
Scientists distinguish:
Spillover
One human becomes infected.
Sustained transmission
Human → Human → Human
This second step is much harder.
For example:
- Rabies infects humans.
- Rabies rarely spreads human-to-human.
Therefore rabies is not considered established in humans.
Lesson 9: Reservoir hosts
A reservoir host is a species that naturally maintains a pathogen.
Examples:
- Bats
- Rodents
- Birds
Reservoir species often show little disease despite infection.
Scientists study reservoirs because they are common sources of future spillovers.
Lesson 10: Why human activity matters
Modern epidemiology emphasizes ecology.
Spillover becomes more likely when humans increase contact with animal hosts.
Examples:
- deforestation
- wildlife trade
- livestock production
- urban expansion
- habitat disruption
The virus doesn't "want" to jump species.
Humans sometimes create opportunities.
Recommended introductory textbook chapters
Fields Virology
The gold standard graduate-level virology text.
Look for chapters on:
- Viral Evolution
- Host Range
- Cross-Species Transmission
Extremely detailed.
Principles of Virology
Probably the best balance between accessibility and rigor.
Excellent coverage of:
- host range
- viral evolution
- zoonotic emergence
Often used in upper-level undergraduate courses.
Medical Microbiology
More clinically focused.
Good overview of zoonotic diseases and transmission.
Excellent educational video lectures
MIT OpenCourseWare – Virology
MIT's biology courses often include lectures on:
- viral evolution
- host range
- emerging infectious disease
Good college-level material.
Khan Academy – Emerging Infectious Diseases
Good high-school to early-college level.
Covers:
- zoonotic diseases
- reservoirs
- transmission chains
HHMI BioInteractive
One of the best free science-education resources available.
Search for:
- Emerging Infectious Diseases
- Spillover
- Viral Evolution
Their animations are excellent and aimed at advanced high school through undergraduate audiences.
A useful mental model
When people hear:
"Virus X jumped from animals to humans"
they often imagine a virus suddenly deciding to infect people.
The textbook model is actually:
Exposure
→ rare infection
→ partial adaptation
→ more infections
→ better adaptation
→ sustained transmission
Most attempts fail.
Most animal viruses never become human viruses.
The ones we hear about are the rare successes.
That's why virologists spend so much time studying spillover events: they are unusual enough to be scientifically interesting, but common enough throughout history to explain diseases like HIV, influenza, SARS, MERS, Ebola, and many others.
What are the types of viruses that are the most likely to spill over?
This is actually a major area of research. Scientists would love to know which viruses are most likely to become the next human pathogen.
The short answer is:
RNA viruses are responsible for most known spillover events into humans.
But there are important reasons why.
The big picture
Researchers who have analyzed emerging infectious diseases consistently find that RNA viruses are disproportionately represented among viruses that jump species and establish themselves in humans.
Examples include:
- Influenza viruses
- Coronaviruses (SARS, MERS, COVID-19)
- HIV (a retrovirus)
- Ebola virus
- Nipah virus
- Hendra virus
- Rabies virus
Why RNA viruses?
1. Higher mutation rates
Most RNA viruses make more copying errors than DNA viruses.
More mutations mean:
- more genetic variation
- more evolutionary "experiments"
- more chances to adapt to a new host
Most mutations are harmful or neutral, but occasionally one helps the virus infect a new species.
2. Large population sizes
Many RNA viruses replicate rapidly and produce enormous numbers of viral particles.
More replication means:
- more opportunities for mutations
- more opportunities for selection
Evolution works faster when there are more "lottery tickets."
3. Some RNA viruses recombine readily
Coronaviruses are a classic example.
When related coronaviruses infect the same host, they can exchange pieces of genetic material.
This creates new genetic combinations that may possess different host ranges.
Which virus families concern scientists most?
Coronaviruses
Examples:
- SARS-CoV
- MERS-CoV
- SARS-CoV-2
Why they're watched:
- large RNA genomes
- recombination
- many animal reservoirs
- especially common in bats
Bats harbor an enormous diversity of coronaviruses.
Influenza viruses
Examples:
- Bird flu (H5N1)
- H7N9
- Swine flu
Why they're watched:
- infect multiple species
- genome segments can reassort
- birds serve as major reservoirs
Influenza's segmented genome allows dramatic genetic shifts.
Paramyxoviruses
Examples:
- Nipah
- Hendra
These viruses have caused deadly outbreaks after spillover from bats through intermediate hosts or direct contact.
Filoviruses
Examples:
- Ebola
- Marburg
These cause severe disease and are believed to have reservoir hosts associated with bats.
Retroviruses
Example:
- HIV
HIV originated from simian immunodeficiency viruses in non-human primates.
Retroviruses don't emerge frequently, but when they do establish themselves, they can become long-term human pathogens.
What animal reservoirs are most important?
Scientists pay particular attention to:
Bats
Why bats matter:
- extremely diverse mammals
- long-lived
- social colonies
- widespread geographic distribution
- host many viruses
Many notable spillover viruses have bat reservoirs.
Rodents
Rodents are important because:
- they live near humans
- populations can become enormous
- they carry numerous viruses
Examples include hantaviruses and arenaviruses.
Birds
Birds are especially important for influenza ecology.
Wild waterfowl are considered the natural reservoir for many influenza A viruses.
Are DNA viruses less likely to spill over?
Generally, yes.
DNA viruses often:
- evolve more slowly
- have tighter host specialization
- depend on complex interactions with host cells
That doesn't mean they can't jump species.
It means they do so less frequently than many RNA viruses.
What makes a virus a spillover risk?
Researchers often look for viruses that have several traits:
✅ Can infect multiple species already
✅ Have RNA genomes
✅ Replicate rapidly
✅ Mutate or recombine readily
✅ Have large wildlife reservoirs
✅ Frequently encounter humans
A virus possessing all six characteristics gets a lot of attention from surveillance programs.
One fascinating thing
A virus can be excellent at infecting humans and terrible at spreading among humans.
Scientists often distinguish:
- Animal → Human infection
- Human → Human transmission
The second step is usually the harder one.
Many spillovers occur every year that never become epidemics because the virus fails at step 2.
That's why epidemiologists worry less about a virus infecting one hunter, farmer, or wildlife worker and much more about whether that virus can sustain a chain of human-to-human transmission.
People are in contact with animals a lot in modern days with markets and population spread into the habitats, why are we not seeing an explosion of spill over from so many interactions and contact?
This is actually one of the strongest arguments against a simplistic understanding of spillover.
If mere contact were enough, we'd be seeing new pandemics constantly.
Humans:
- raise billions of chickens, pigs, and cattle,
- hunt wildlife,
- keep pets,
- work in zoos,
- study bats,
- visit live animal markets,
- clear forests,
- and live alongside rodents.
Yet most animal viruses never become human viruses.
The reason is that contact is only the first barrier of many. A spillover virus has to win a series of biological "lotteries" in a row.
Think of it as a series of filters
A virus must:
- Be present in the animal.
- Be shed from the animal.
- Survive long enough to reach a human.
- Reach the right tissue in the human.
- Bind to human cells.
- Replicate in human cells.
- Evade the immune system.
- Exit the infected human.
- Infect another human.
- Continue doing that repeatedly.
Fail at any one step and the chain ends.
We probably are seeing lots of spillovers
Here's the fascinating part:
Many researchers think spillovers happen far more often than people realize.
What is rare is not necessarily:
Animal → Human infection
What is rare is:
Animal → Human → Human → Human
In other words, the vast majority of spillovers are probably dead ends.
A hunter, farmer, veterinarian, wildlife worker, or market vendor may occasionally acquire an animal virus that infects a few cells, perhaps even causes mild illness, and then goes nowhere.
Scientists call these dead-end spillovers.
Why don't we notice them?
Because most are likely:
- asymptomatic,
- mild,
- misdiagnosed,
- or never tested.
Before modern sequencing, we would have had almost no way to know many of them occurred.
In fact, modern surveillance is finding previously unknown viruses in people more frequently than ever before because sequencing technology has become so powerful.
Human-to-human transmission is the hardest step
This is where many discussions go wrong.
People imagine that once a virus infects a person, the hard part is over.
Often the opposite is true.
A virus may be able to infect a human cell but still be terrible at spreading between humans.
Rabies is a good example:
- Animal → Human transmission occurs.
- Human → Human transmission is extraordinarily rare.
So rabies repeatedly spills over but never becomes a human pandemic virus.
Why are bats and birds watched so closely?
Not because every bat virus is a threat.
It's because:
- They host many viruses.
- They live in large populations.
- They move long distances.
- They have frequent opportunities to contact other species.
A large reservoir creates more "attempts" at spillover. Even if each attempt has a tiny chance of success, enough attempts eventually matter.
An analogy
Imagine trying to open a vault that requires ten combination locks in a row.
Human-animal contact only gets you through the first lock.
The virus still has to pass the remaining nine.
That is why researchers can simultaneously say:
"Human contact with animals is increasing."
and
"Pandemic-capable spillovers remain rare."
Both statements are true.
The really interesting modern view
One of the newer ideas in spillover science is that we may be looking at the wrong thing when we focus only on the moment a virus jumps species.
Researchers increasingly view spillover as a process, not a single event:
- Repeated exposure.
- Occasional dead-end infections.
- Limited adaptation.
- More spillovers.
- Better adaptation.
- Sustained transmission.
A successful new human pathogen may have had many failed attempts before the one that finally "took off."
That's one reason scientists pay attention not just to major outbreaks, but also to small, seemingly insignificant spillover events—they may be glimpses of a virus trying, and usually failing, to cross all those barriers.
Ok, about Covid 19. It is a SARS-Cov virus. What is the best origin so far?
over, probably from a bat-related coronavirus, potentially through an intermediate animal host.
But—and this is important—the evidence does not establish exactly which animal, exactly where, or exactly when the first human infection occurred. The WHO's independent scientific advisory group (SAGO) concluded in 2025 that the weight of available evidence favors zoonotic spillover, while also saying that a laboratory-related incident cannot be completely excluded because important information remains unavailable.
Why does the natural-spillover hypothesis currently have the strongest evidence?
There are several independent pieces that fit together.
1. The earliest known cases geographically clustered around the Huanan market in Wuhan.
The earliest pandemic cases were strongly associated with the Huanan Seafood Wholesale Market, which also sold live wildlife. That doesn't by itself prove the market was where the virus first jumped into humans—but it is an important epidemiological clue.
2. SARS-CoV-2-positive environmental samples were found in areas where susceptible wildlife was present.
Subsequent analysis of the market samples found DNA from animals including raccoon dogs, civets and bamboo rats in samples that also contained SARS-CoV-2 genetic material. A 2024 Cell paper found particularly interesting associations around a wildlife-selling stall.
But here's an important caveat:
Those samples do NOT prove that one of those animals was infected.
The samples were collected after human transmission was already occurring. Therefore, SARS-CoV-2 could have contaminated the environment from infected humans, animals, or both. Researchers cannot reconstruct the direction of transmission from those samples alone.
That's a really important piece of scientific honesty.
3. The virus has close relatives in bats.
The closest known relatives of SARS-CoV-2 have been found in bats in China and Laos. But none of the currently known bat viruses is close enough to be identified as the direct ancestor.
That actually makes sense under a natural-emergence model: we would expect the immediate precursor to exist somewhere, but we haven't necessarily sampled the right animal population at the right time.
What about the laboratory-origin hypothesis?
This is where I would not tell you, "That's been completely disproven."
It hasn't.
There are actually two different laboratory hypotheses that should be separated:
A. Accidental infection during laboratory work
For example, researchers could have encountered a naturally occurring bat coronavirus during field collection or laboratory research, followed by an accidental infection and subsequent spread.
This remains possible.
WHO/SAGO specifically said it could not adequately evaluate this possibility because information about laboratory activities and biosafety conditions in Wuhan has not been fully provided.
B. Deliberate genetic engineering
That's the much stronger claim:
Scientists intentionally modified a coronavirus and it escaped.
Here the evidence is considerably weaker.
SAGO examined the genomic evidence and concluded that the available genome does not provide evidence that SARS-CoV-2 was genetically engineered. Its genetic characteristics can be explained through naturally occurring mutation and recombination.
So I'd separate those claims very carefully:
| Hypothesis | Evidence currently |
|---|---|
| Natural animal → human spillover | Best-supported |
| Accidental laboratory-related infection | Not excluded |
| Deliberately engineered virus | No convincing genomic evidence |
| Deliberately released virus | No good evidence |
And this connects directly to what we were just discussing
Remember our discussion about species jumping?
SARS-CoV-2 actually fits the model remarkably well.
You have:
Animal coronavirus reservoir
↓
Genetic variation among animal coronaviruses
↓
Opportunity for contact with humans
↓
Cross-species transmission
↓
Adaptation to human cells
↓
Human-to-human transmission
The problem is that we don't have the smoking gun—the actual animal carrying the immediate precursor and evidence showing that animal infected the first human.
That's why I'd describe the natural-origin hypothesis as the best-supported explanation, rather than a proven historical fact.
And that's also why the Huanan market evidence is so interesting. The 2024 genetic analysis gives us something much closer to the kind of evidence you were asking about earlier: actual viral sequences + environmental sampling + animal DNA + geographic distribution + phylogenetics.
If you want, I think the next thing we should do is examine the SARS-CoV-2 genome itself—what scientists compared it to, what "closest relative" actually means, and what features of its sequence argue for or against natural evolution versus laboratory manipulation. That's a perfect continuation of the virus-sequencing lesson we started with.
Is there a layer here of how uncooperative China is with the U.S. and the world? Is there a strong possibility that they are not forthcoming with information? I still don't think they are being very truthful about their Covid 19 Death toll.
es. There is a real layer of this, and I think it's important to distinguish "China is lying" from "China has not provided enough information for outsiders to independently verify important claims." The second statement is very well supported; the first is sometimes justified in particular instances, but is harder to establish as a blanket claim.
On the origins question: there really is missing information
This isn't merely a suspicion from U.S. intelligence agencies or internet commentators. In its June 2025 assessment, WHO's Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) explicitly said that China had not provided information it had requested, including:
- hundreds of early-pandemic human genetic sequences,
- more detailed information about animals sold at Wuhan markets,
- information concerning laboratory work conducted in Wuhan,
- and laboratory biosafety information.
That's significant.
And SAGO's conclusion was essentially:
We have enough evidence to say zoonotic spillover is currently the best-supported explanation, but we don't have enough information to completely evaluate every possible origin.
So "natural origin is best supported" and "China has withheld information relevant to determining the origin" can both be true simultaneously.
China disputes that characterization and says it has been open and has shared information.
Your question about the death toll is a little different
Here I'd be more cautious.
I think it's reasonable to say:
China's official COVID death count almost certainly does not represent the total number of deaths caused by the pandemic.
But that doesn't necessarily mean:
"China deliberately lied about the number of people who died."
There are several reasons official COVID death counts can be substantially lower than the actual mortality impact.
The biggest problem is the definition of a "COVID death."
During different periods China used relatively restrictive definitions for counting COVID deaths. For example, during the huge outbreak following the abandonment of zero-COVID in late 2022, China initially reported only deaths occurring in hospitals among people who died with COVID-related pneumonia or respiratory failure.
That means somebody who:
- had COVID,
- developed a cardiovascular event,
- died at home,
might not appear in the official COVID death count.
That's one reason excess mortality is so useful.
And this is where the numbers get interesting
Researchers can ask:
How many people normally die in China during this period of the year?
Then compare that with:
How many actually died?
The difference is excess mortality.
It doesn't automatically equal COVID deaths—lockdowns, medical-care disruption, economic effects, etc., can influence mortality—but a huge unexplained mortality spike is extremely difficult to make disappear simply by changing the definition of COVID.
For Wuhan during the initial outbreak, researchers using Chinese mortality surveillance data found 56% excess mortality in the three districts studied, with an especially large increase in pneumonia deaths.
And the situation after China abandoned zero-COVID is even more striking.
One study estimated approximately 637,000 excess deaths in China between December 2022 and February 2023, compared with the government's reported 83,150 in-hospital COVID deaths during that period. The authors explicitly caution that their estimate includes deaths outside hospitals and deaths that Chinese authorities didn't classify as COVID.
That's a very large discrepancy.
But I would not take that 637,000 number and say:
"China had exactly 637,000 COVID deaths."
That's not what the study demonstrated.
It's evidence that the official count probably substantially underestimated the pandemic's mortality impact, not a precise alternative death certificate database.
And there's an even bigger methodological point
This is why I wouldn't focus exclusively on China.
WHO's excess-mortality analysis estimated approximately 14.8 million excess deaths worldwide during 2020–2021, compared with about 5.4 million officially reported COVID deaths during that period.
That's not evidence that every country was lying.
It demonstrates that official COVID death counts are an imperfect measurement of the pandemic's total mortality burden.
Some countries had:
- inadequate testing,
- limited death certification,
- deaths at home,
- changing definitions,
- overwhelmed medical systems,
- or poor mortality surveillance.
China had some particularly serious problems with transparency and reporting, but the underlying statistical problem isn't uniquely Chinese.
So I'd separate your two suspicions
"Is China withholding information about the origin of SARS-CoV-2?"
Yes, there is strong evidence that important information requested by WHO/SAGO has not been provided. That's an established fact, not speculation.
"Could China therefore be hiding something important about the origin?"
Absolutely possible.
But we don't know what that missing information would show.
It could potentially strengthen the natural-spillover hypothesis, strengthen a laboratory-associated hypothesis, or simply fill in historical gaps without changing the conclusion.
That's why withholding evidence is different from evidence of guilt.
"Is China's official COVID death count probably too low?"
Yes, I think the evidence strongly supports that conclusion.
The enormous excess mortality during the 2022–23 wave is particularly difficult to reconcile with the official COVID death count.
"Does that prove China intentionally falsified the numbers?"
No.
It establishes that the official number is an incomplete measure of the pandemic's mortality, but determining how much was deliberate suppression versus definitions, reporting practices, overwhelmed systems, and ordinary measurement problems requires additional evidence.
And honestly, this is exactly the kind of situation where I think your approach of following the evidence rather than choosing a side is useful.
There's a temptation to say either:
"China says it was transparent, therefore everything is fine."
or:
"China is an authoritarian government, therefore everything they say is false."
Neither is good science.
The scientifically defensible position is:
We know some important data haven't been made available. We can therefore place limits on how confident we can be about certain conclusions. Where independent mortality data exist, we should use them rather than relying exclusively on government-reported case and death counts.
And that same principle is useful when we get into the lab-leak question: we can look separately at the positive evidence for natural spillover, the positive evidence for laboratory involvement, and the missing evidence that prevents us from resolving the question definitively. That gets much more interesting than simply asking "Was it a lab leak?"
Well, that is too political and semantic for me. Let's go back to virology - Is there any establish ethics committee/board or ethics policy on virus experimentation?
Yes. There is an established system for this, and it is actually quite a good rabbit hole if you want to understand how scientists are supposed to govern dangerous virus research.
One important distinction first: there isn't one universal "virus ethics board" that approves every virus experiment worldwide. Instead, there are several overlapping layers of ethics, biosafety, biosecurity, and dual-use oversight.
The basic structure
Think of it roughly like this:
Scientist proposes experiment
↓
Institutional review
↓
Biosafety / animal / human-subject committees as applicable
↓
Government or funding-agency requirements
↓
Special review for unusually dangerous or potentially pandemic-enhancing work
The committees aren't all asking the same question.
| Oversight | Main question |
|---|---|
| IRB | Are human research subjects being treated ethically and safely? |
| IACUC | Is animal experimentation ethically and humanely justified? |
| IBC | Can this biological work be conducted safely? |
| Biosecurity/DURC review | Could the research be misused or create an unusually dangerous pathogen? |
| Government regulators/funders | Should this particular high-risk work be permitted or funded? |
The Institutional Biosafety Committee (IBC) is probably the one you're looking for first. NIH describes IBCs as a critical component of biosafety oversight; they review and oversee research involving biohazardous materials.
There's also a specific concept called "dual-use research"
This is particularly relevant to viruses.
Dual-use research means research that can have legitimate scientific/public-health benefits but whose knowledge, methods, or products could potentially be misused to cause harm.
For example, there's an obvious legitimate reason to study how a virus infects cells:
"If we understand this mechanism, perhaps we can develop a drug that blocks it."
But the same general knowledge could potentially be useful for someone trying to make a pathogen more dangerous.
That's the ethical dilemma.
The U.S. has a federal advisory body specifically devoted to this problem: the National Science Advisory Board for Biosecurity (NSABB). It advises the government on biosafety, biosecurity, and dual-use research.
And there's a particularly controversial category: "gain-of-function"
This is where the conversation gets interesting.
Not every experiment that changes a virus is "gain-of-function" in the dangerous sense. Scientists routinely modify viruses for legitimate research.
The concern is research that could produce a pathogen with characteristics such as:
- substantially increased pathogenicity,
- increased transmissibility,
- increased ability to evade immunity,
- or other properties that could create serious public-health consequences.
The U.S. has developed specific policies for evaluating research involving potential pandemic pathogens and dual-use research.
And the rules are not static.
That's actually important to our earlier discussion about scientific mistakes. The U.S. government has repeatedly changed its oversight framework as researchers and policymakers have identified weaknesses.
And there has been a major policy change recently
Because we're talking about this in 2026, there's a current wrinkle worth knowing.
In 2025, the U.S. government paused/suspended funding for research falling under its definition of dangerous gain-of-function research and began developing a new oversight framework.
Then, in July 2026, NIH issued a new U.S. Government Policy for Stopping High-Risk Life Sciences Research, which includes an explicit prohibition on dangerous gain-of-function research.
So if you find older videos talking about the "2017 P3CO framework" or the "2024 DURC/PEPP policy," be aware that the U.S. policy landscape has changed since then.
There's an international layer too
The World Health Organization has its own framework for responsible life-sciences research.
WHO's 2022 framework explicitly addresses:
biosafety + biosecurity + dual-use research
and describes biorisk management as a shared responsibility among researchers, institutions, governments, funders, publishers, and other stakeholders.
WHO also published updated Laboratory Biosecurity Guidance in 2024, covering risk management throughout the life cycle of high-consequence biological materials—from collection and transportation through storage and experimentation. It specifically emphasizes institutional biosafety committees and national/institutional regulatory oversight.
And here's something I think you'll appreciate given what we've been studying
The ethical system isn't simply:
"Is this experiment scientifically interesting?"
It is supposed to ask:
"Is the scientific benefit worth the biological risk we're creating?"
And potentially:
"Can we obtain the same information using a safer experiment?"
That's a risk-versus-benefit framework.
The NSABB's own guidance specifically tells researchers to consider whether the knowledge or products could be deliberately misused, minimize dangerous elements of experimental design where possible, and weigh unavoidable risks against the benefits.
So yes—there is an established ethical/biosafety infrastructure.
But here's where I think this gets really interesting for your COVID investigation:
There are actually three different questions that often get conflated:
1. Was the experiment scientifically legitimate?
2. Was it conducted safely?
3. Should the experiment have been allowed in the first place given the potential consequences?
Those are three different judgments.
And if you want to understand the controversy surrounding coronavirus research in Wuhan, NIH, EcoHealth Alliance, gain-of-function research, etc., we should learn this oversight system first. Then we can examine specific experiments and ask which committee was supposed to review them, what rules applied at the time, and whether those rules were actually followed.
That would give us a much better framework than starting with the lab-leak argument itself.
I have read the "Hot Zone" and "Demon in the Freezer" by Richard Preston. What kind of research are they doing on smallpox and Ebola? Is it beneficial to society?
Yes. And The Hot Zone and The Demon in the Freezer are actually excellent books to use as a springboard into this question, because Preston gives you the dramatic human story, while the underlying research has a much more specific purpose.
The short answer is:
Yes, much of the research on Ebola and smallpox is highly beneficial to society—but smallpox is an especially interesting ethical case because the disease has been eradicated, yet scientists deliberately retain a tiny amount of live variola virus for research.
And that's exactly where the question of "Is the risk of doing the research worth the benefit?" becomes very real.
🦠 Ebola: Why study something so dangerous?
With Ebola, the benefit is fairly straightforward.
Researchers study the virus to understand:
- how it causes disease,
- how it enters cells,
- how the immune system responds,
- how to diagnose infection quickly,
- how long infectious material can persist in survivors,
- how to develop vaccines,
- and how to develop treatments.
The research has produced very tangible benefits.
For example, during the 2014–2016 West African outbreak, researchers conducted clinical trials of Ebola vaccines and treatments. One of those efforts eventually contributed to the development of ERVEBO, an FDA-approved Ebola vaccine. The United States now also has two FDA-approved monoclonal-antibody treatments for Ebola caused by Orthoebolavirus zairense.
And there's a particularly good example of research translating directly into lives saved.
During the 2018–2019 Ebola outbreak in the Democratic Republic of the Congo, researchers conducted a randomized trial comparing experimental treatments. mAb114 and REGN-EB3 produced substantially better survival than the comparator treatment, leading the independent monitoring board to recommend stopping the trial and giving the more effective treatments to subsequent patients.
That's a pretty compelling example of why you study a dangerous virus before and during an outbreak.
But smallpox is much more interesting
Smallpox presents a completely different ethical problem.
There is no naturally circulating smallpox anymore.
WHO declared smallpox eradicated in 1980, making it the only human infectious disease successfully eradicated worldwide.
So you could reasonably ask:
"If we've gotten rid of it, why on Earth would we keep the virus?"
That's been debated for decades.
There are currently only two authorized repositories of live variola virus:
- CDC in Atlanta
- VECTOR in Russia
And WHO oversees research involving the live virus.
What are they trying to accomplish?
The basic argument for retaining it is preparedness.
Scientists want to make sure that if smallpox ever reappeared—whether through an accidental release, an unknown remaining natural reservoir, or deliberate release—we would have the ability to respond.
Research has included:
Better vaccines
The original smallpox vaccines are effective, but they aren't ideal for everyone because they use live vaccinia virus and can cause serious complications in certain people.
So researchers have developed newer, safer vaccines.
Antivirals
Researchers want drugs that can actually treat smallpox after someone becomes infected.
That's important because vaccination after exposure isn't always sufficient.
Diagnostics
Scientists need to be able to distinguish smallpox from other orthopoxvirus infections quickly.
Understanding immunity
Researchers study what kind of immune response protects against smallpox and how long that protection lasts.
Understanding related viruses
This has become particularly relevant because of mpox.
The research isn't just about a hypothetical smallpox outbreak anymore. Work on orthopoxviruses can contribute to preparedness against other members of the same viral family. WHO explicitly identifies benefits for mpox prevention and response.
And here's the part that connects beautifully to what we've been discussing
WHO doesn't simply say:
"Scientists want to study smallpox, so let them."
There is a specific international oversight system.
The WHO Advisory Committee on Variola Virus Research (ACVVR) oversees the research program. It reviews proposed work involving live variola virus, considers research priorities, and oversees issues surrounding the two repositories.
And WHO conducts biennial biosafety and biosecurity inspections of the two repositories. Those inspections are performed by independent international experts using recognized biosafety and biosecurity standards.
There's even a very strong restriction on what researchers can do with variola DNA. WHO guidance prohibits genetic engineering of variola virus and attempts to produce live virus from DNA.
So this is a pretty extraordinary situation:
The world eradicated the disease, retained a tiny amount of the causative virus, and then created an international system specifically to decide whether continuing to possess it is justified.
And scientists actually disagree about whether it's worth keeping
This is something I think is really important for understanding scientific ethics.
It's not a case where everyone agrees that retaining live smallpox is obviously necessary.
WHO has convened independent expert groups to examine exactly this question.
For example, in a 2013 review, a majority of the independent experts concluded that live variola virus was no longer necessary for additional genome sequencing, animal models, diagnostics, or development of additional vaccines—but there was disagreement over whether live virus was still needed for antiviral development.
Other experts have argued that retaining it is justified because we don't know what future threats or technological developments might make additional research valuable.
The World Health Assembly ultimately decided to continue retaining the stocks and, in 2024, authorized continued research aimed at developing countermeasures and preparedness. The issue is scheduled for another review in 2029 or sooner if necessary.
And there's a fascinating modern example
The 2024 WHO research program included proposed work involving:
- improved diagnostics,
- less-reactogenic vaccines,
- antiviral testing,
- monoclonal antibodies,
- and even evaluation of mRNA vaccine approaches against variola.
That ties directly back to our mRNA discussion.
Researchers aren't saying:
"Let's play with smallpox because we can."
They're asking:
"If this virus ever returns, can we have the tools ready before people start dying?"
But there is a legitimate counterargument:
"The virus is eradicated. Every experiment involving live variola introduces some risk. Couldn't we obtain the same information without keeping the live virus?"
That's not an anti-science argument. That's a legitimate scientific-policy question, and scientists have been arguing about it for decades.
And this is where Demon in the Freezer gets especially interesting
Preston's book is largely about smallpox, biological security, and the terrifying possibility of deliberate release.
But the modern situation is considerably more nuanced than:
"We keep smallpox because terrorists might get it."
There are really three competing goals:
1. Eliminate the virus completely.
2. Keep enough virus to develop better defenses against it.
3. Make absolutely certain that the research itself doesn't create a greater danger than the threat it is intended to protect against.
That third point is exactly why smallpox is one of the best examples we could use to study the ethics of virus experimentation.
And I think there's a really good next step here: we could take the actual research being done on live variola today and go through it project-by-project—not the experimental procedures themselves, but what scientists are trying to learn, what benefit they expect, what risks the WHO committee identified, and why each project was considered worth doing.
That would give you a real-world example of the ethical framework we were just discussing.
Could there be a chance that there would be unintentional "gain of Function" while working with these viruses at labs?
Yes. Absolutely—and this is one of the reasons biosafety exists in the first place. It doesn't require scientists to deliberately design a virus to become more dangerous.
There are actually two different things we should separate:
1. Accidental selection for a new property
A virus is evolving while it replicates. If you repeatedly grow a virus under particular conditions, variants that happen to reproduce better under those conditions can become more common.
That's evolution happening in the laboratory rather than in nature.
A mutation could therefore arise without anyone intending to create it. Whether that counts as "gain of function" depends on the definition being used. WHO defines gain-of-function broadly as a modification that results in a new or enhanced property, but notes that the term is often used specifically for enhanced pathogenic characteristics.
2. An accidental laboratory release
That's a separate problem.
Even if researchers never intentionally make the virus more dangerous, an infectious virus could theoretically:
change in the lab → infect a researcher → leave the laboratory → spread into the community.
WHO explicitly recognizes both unintentional exposure/release and deliberate misuse as risks associated with high-consequence research.
And this isn't purely theoretical as a category of risk. Laboratory-acquired infections have occurred historically. WHO notes that SARS-CoV infections acquired in laboratories in Singapore, Taipei, and Beijing during 2003–2004 prompted reviews and improvements in biosafety policies.
But there's an important wrinkle
"A virus mutated in the laboratory" doesn't automatically mean "the scientists accidentally created a supervirus."
Viruses mutate constantly.
Suppose scientists are studying an ordinary virus and a mutation occurs that makes it replicate slightly better in their particular cell culture. That's technically a change in phenotype, but it doesn't necessarily make the virus:
- more transmissible between humans,
- more pathogenic,
- better adapted to humans,
- or more dangerous outside that laboratory environment.
This is one reason the terminology around gain-of-function gets confusing.
The National Academies' review points out that gain-of-function and loss-of-function experiments are ordinary tools of molecular biology; the controversial category is the subset involving changes that could significantly increase pathogenicity or transmissibility.
And this is why the oversight question you asked about earlier matters
Modern biosafety isn't based on the assumption that:
"Scientists are careful, so nothing will go wrong."
It's based on almost the opposite assumption:
"Scientists are human, biological systems are unpredictable, and equipment and procedures can fail—so we need layers of protection."
WHO's current laboratory biosecurity guidance specifically addresses research involving high-consequence pathogens and calls for risk assessment, institutional oversight, and national/international regulatory mechanisms.
And the United States has become substantially more restrictive about the highest-risk research. As of July 28, 2026, the new U.S. Government Policy for Stopping High-Risk Life Sciences Research explicitly prohibits federal support for defined categories of dangerous gain-of-function research and adds additional review requirements for other high-risk research.
So your basic intuition is correct:
Yes, unintended changes can occur while scientists are working with viruses.
But there are three separate questions:
Could the virus change?
→ Yes. That's normal viral evolution.
Could it acquire a property that makes it more concerning?
→ Yes, in principle.
Could that virus then escape the laboratory and cause an outbreak?
→ Yes, that is a recognized biosafety risk.
The probability of the complete sequence is another question, and that's what the layers of containment, experimental design, monitoring, and oversight are intended to reduce.
And this gives us a really useful next step for understanding the COVID laboratory-origin debate: we should look at what "gain of function" actually means in practice, because the phrase is used for everything from completely routine virology experiments to genuinely high-risk pathogen modification. Those are not equivalent.
Now vaccines in general - First, I know that in the past, vaccine development had its issues, but for today, are all new vaccines that do not have an established vaccine tested against a placebo?
Yes—but there is an important qualification: a new vaccine does not automatically have to be tested against an inert sugar-water-type placebo. What it does need is a scientifically and ethically appropriate control/comparator.
The distinction is important.
If there is no existing vaccine for the disease
A placebo-controlled randomized trial is generally an appropriate—and often preferred—design.
For example:
New vaccine → vaccinated group
Placebo → control group
Then researchers can compare:
- adverse events,
- infections,
- disease,
- hospitalization,
- immune responses,
- etc.
WHO specifically says placebo use is clearly acceptable when no safe and effective vaccine exists for the disease being studied.
The FDA likewise describes placebo as one of the standard controls used during vaccine development. Phase 2 and Phase 3 studies use controls that can include a placebo, an already-approved vaccine, or another substance.
But what if an effective vaccine already exists?
This is where things change.
Suppose Vaccine A already protects people against Disease X, and you're developing Vaccine B for Disease X.
It can be ethically problematic to give people nothing simply so you can have a placebo group.
Instead, researchers can do:
New vaccine → Vaccine B
Existing vaccine → Vaccine A
That's called an active-controlled trial.
Now the question becomes:
"Is the new vaccine at least as effective and safe as the vaccine we already have?"
This can be a non-inferiority trial, or sometimes a superiority trial if researchers expect the new vaccine to be better.
WHO guidance says that when a licensed, effective vaccine exists, it would generally be the comparator of choice, with exceptions requiring justification and ethical review.
There's also a clever third option
Sometimes researchers use an unrelated vaccine as the control.
For example:
New COVID vaccine → experimental group
MenACWY meningococcal vaccine → control group
The meningococcal vaccine doesn't protect against COVID, but it gives participants an actual vaccination rather than an inert injection.
This was actually done in the AstraZeneca COVID-19 vaccine Phase 3 trial. WHO describes the trial as randomized and notes that MenACWY served as the control.
So, to your exact question:
"Are all new vaccines that don't have an established vaccine tested against a placebo?"
Not necessarily, but placebo-controlled trials are a major and often appropriate design when no effective vaccine exists.
The bigger principle is:
A new vaccine needs an appropriate control group, but "appropriate control" does not always mean an inert placebo.
And there's an important distinction from some of the claims you've been investigating:
"It wasn't compared with saline placebo" ≠ "it wasn't properly tested."
You have to ask what the comparator was and why researchers chose it.
FDA says Phase 3 vaccine studies generally involve thousands of people and compare the vaccine with a control such as a placebo; WHO similarly describes Phase 3 as comparing vaccinated participants with a comparator group.
One more important piece
Even a placebo-controlled trial isn't the end of vaccine testing. Before human trials, vaccines undergo preclinical testing, and after approval they continue to be monitored for safety and effectiveness. WHO explicitly describes post-approval monitoring as part of vaccine safety surveillance.
So if we're trying to evaluate a particular vaccine, I'd use this checklist:
1. Was it randomized?
2. Was it blinded?
3. What was the control?
4. Why was that control chosen?
5. How large was the trial?
6. What outcomes were actually measured?
7. How long were participants followed?
8. What happened to the control group after the trial?
9. What did later studies find?
That is a much better way of evaluating the claim "this vaccine wasn't tested properly" than simply asking whether the trial used saline placebo.
An unrelated vaccine as a control would basically be like a vaccinated vs. Unvaccinated group?
Not quite. It's closer to "new vaccine vs. another vaccination" than "vaccinated vs. unvaccinated."
For example:
- Group A: gets the new COVID vaccine.
- Group B: gets an unrelated meningococcal vaccine.
- Neither participant nor investigator may know which injection they received.
Both groups are therefore vaccinated, but only Group A receives protection against the disease being studied.
Why would researchers do that?
An unrelated vaccine is an active control. It helps control for things that wouldn't be controlled by simply comparing vaccinated people with completely unvaccinated people, such as:
- the physical act of getting an injection,
- reactions to the injection,
- some nonspecific immune/inflammatory responses,
- participant expectations,
- and differences in how closely people interact with the healthcare system.
So the comparison is essentially:
Does the new vaccine produce different outcomes than receiving another vaccine?
rather than:
Does vaccination produce different outcomes than receiving nothing?
Compare the three designs
| Experimental group | Control group | What you're primarily asking |
|---|---|---|
| New vaccine | Saline/placebo | What does this vaccine do compared with no vaccine? |
| New vaccine | Existing vaccine | Is the new vaccine as good/better than the established one? |
| New vaccine | Unrelated vaccine | What happens with the new vaccine compared with another vaccination? |
| New vaccine | No intervention | What happens compared with simply receiving nothing? |
And there's an important limitation to your analogy:
An unrelated-vaccine control cannot tell you everything that a truly unvaccinated group could tell you. If both groups experience an outcome at similar rates, you can't necessarily conclude that vaccination has no effect—you've shown that the new vaccine didn't differ substantially from the control vaccine for that outcome.
That's why the research question determines the appropriate control.
And this gets particularly interesting when we start looking at the COVID vaccine trials, because different COVID vaccines used different control groups. We can go through Pfizer, Moderna, AstraZeneca, J&J, etc., and look at exactly what each trial used and why.
Real quick. . . It is a favorite topic of anti vaccine groups that none of the childhood vaccines had ever been tested against a placebo. Is that true?
No. That claim is false as stated. It takes a real observation—many established childhood vaccines were not tested against an inert saline placebo in their pivotal modern trials—and turns it into the much stronger claim that they were never tested against placebo at all.
There are several important examples where childhood vaccines were tested in randomized placebo-controlled trials. The American Academy of Pediatrics gives examples, and WHO explicitly recognizes placebo-controlled vaccine trials as a standard trial design.
For example:
- Polio vaccine: the famous 1954–55 Salk vaccine field trial was randomized, blinded, and included placebo controls. Some children in the placebo group developed polio and died—one reason today's ethical standards around placebo controls are much stricter.
- Early MMR vaccines: placebo-controlled trials were conducted. Later versions were generally compared with existing vaccines rather than an inert placebo.
- Rotavirus vaccines: products such as Rotarix and RotaTeq were evaluated in large randomized placebo-controlled trials.
- There are also placebo-controlled trials involving Hib, pneumococcal, and other childhood vaccines, depending on the particular vaccine and formulation. WHO's review provides examples of vaccines being tested against placebo even after related vaccines already existed.
Where the claim gets its kernel of truth
If someone says:
"Not every childhood vaccine on today's schedule was originally tested against an inert placebo."
That's much closer to the truth.
Once an effective vaccine already exists, researchers often shouldn't give children a placebo and leave them unprotected merely to make a cleaner experiment. WHO's ethics guidance specifically says placebo is clearly acceptable when no effective vaccine exists, but can be ethically unacceptable when an effective, accessible vaccine exists and withholding it creates meaningful risk.
Instead, the new vaccine can be compared with:
New vaccine ↔ established vaccine
That's still a randomized controlled trial. It's just an active-controlled trial rather than a placebo-controlled trial.
So if somebody says:
"Childhood vaccines have never been tested against placebo."
No. That's demonstrably wrong.
If they say:
"Some vaccines currently on the childhood schedule were licensed based on trials using an existing vaccine or another comparator rather than an inert placebo."
Yes. That's true.
And I think this is an important distinction for what you're investigating, because "no saline placebo" and "no controlled clinical trial" are two completely different claims.
Do you have a link to the chart or resource of all the childhood vaccines and how they were tested with placebos or similar?
Yes. I found something much closer to what you're asking for than a generic vaccine-safety page.
Best resource: CDC's 2025 ACIP presentation
The CDC actually has an ACIP presentation that goes through every stand-alone routine childhood vaccine on the U.S. schedule and the pivotal trial used for FDA licensure, including what the control group was.
CDC/ACIP presentation — Controls, safety durations, statistical power (PDF)
This is probably the resource you're looking for. It specifically addresses the question:
Was the pivotal trial placebo-controlled, or did it use another vaccine/control?
And it gives FDA source citations for the individual vaccines.
I'd also bookmark the WHO guideline
WHO's Guidelines on clinical evaluation of vaccines: regulatory expectations is excellent for understanding why different controls are used.
WHO — Guidelines on clinical evaluation of vaccines
It explicitly explains that a new vaccine can be tested against:
- an inert placebo,
- a vaccine that doesn't protect against the disease being studied, or
- an already licensed vaccine against the same disease.
It also explains why a placebo may not be appropriate once an effective vaccine already exists.
And here's the current CDC childhood-vaccine list
If we're going to work through them systematically, this is the authoritative list of what's currently included in the U.S. child/adolescent schedule:
CDC — Child & Adolescent Immunization Schedule
It includes Hep B, rotavirus, DTaP, Hib, pneumococcal, polio, MMR, varicella, hepatitis A, HPV, meningococcal, influenza, etc.
I think we should do something useful with these
Rather than just give you the links, we can build our own table together from the primary FDA trial records:
| Vaccine | Pivotal trial | Placebo? | Control type | Randomized? | Blinded? | Size | Follow-up |
|---|---|---|---|---|---|---|---|
| Hepatitis B | |||||||
| Rotavirus | |||||||
| DTaP | |||||||
| Hib | |||||||
| Pneumococcal | |||||||
| Polio | |||||||
| MMR | |||||||
| Varicella | |||||||
| Hepatitis A | |||||||
| HPV |
That would let us test the "childhood vaccines were never placebo tested" claim vaccine-by-vaccine instead of relying on either pro- or anti-vaccine summaries.
And importantly, I'd distinguish the original vaccine's pivotal trial from later versions/formulations. Those can have completely different controls.
I will have to build that chart latter. Give me the history of the autism claim and vaccines and how it's changed since the original claim was made....
Yes. This has a surprisingly long history, and the claim has changed substantially over time. One of the most useful things to understand is that there wasn't actually one vaccine-autism claim. There were several related claims that emerged at different times—MMR → autism, thimerosal → autism, and eventually "the entire childhood vaccine schedule" → autism.
Here's the history in roughly chronological order.
1. Autism was recognized long before the modern vaccine schedule
Autism wasn't discovered in the 1990s.
Leo Kanner described what he called "early infantile autism" in 1943, and Hans Asperger described a related pattern in 1944.
This matters because the vaccine hypothesis sometimes begins with:
"Autism appeared when vaccines increased."
But autism was being clinically recognized decades before the childhood immunization schedule became large.
The really interesting historical question became why diagnoses appeared to be increasing so rapidly, particularly from the 1980s onward.
That question was—and remains—much more complicated than simply counting diagnosed children.
2. The first major vaccine-autism controversy: MMR
The modern vaccine/autism controversy really exploded in 1998.
British physician Andrew Wakefield and 12 colleagues published a paper in The Lancet describing 12 children with developmental problems and gastrointestinal symptoms.
The paper did not actually conduct a controlled trial showing that MMR caused autism.
It was essentially a case series.
But the paper reported that some parents said their children's behavioral/developmental symptoms appeared after MMR vaccination.
That temporal association became the foundation for a much larger claim.
The paper suggested that the observations warranted further investigation into a possible connection between MMR, intestinal disease, and developmental regression.
The media coverage, however, turned this into:
MMR causes autism.
And Wakefield himself publicly promoted that interpretation.
3. The problem with the original paper became much worse
This is an important part of the story because it illustrates something you've been asking about throughout this whole discussion:
Science can catch bad research—but sometimes it takes years.
Subsequent investigation found serious problems with Wakefield's work.
Among other things, the children were not actually a consecutive series of cases, as the paper represented them, and there were serious discrepancies between the medical records and the published descriptions.
The UK General Medical Council ultimately found Wakefield guilty of serious professional misconduct.
In 2010, The Lancet completely retracted the paper.
And there's an additional layer that is particularly important: investigators uncovered undisclosed financial conflicts of interest surrounding Wakefield's work, including involvement with lawyers pursuing litigation against vaccine manufacturers. The National Academies summarizes the subsequent findings and the retraction history.
So today, the 1998 paper isn't simply regarded as "an early study that turned out to be wrong."
It was retracted because the underlying research was found to contain serious misrepresentations.
4. But the scientific question didn't end with Wakefield
This is where I think it's important not to make the opposite mistake.
Scientists didn't simply say:
"Wakefield was fraudulent, therefore the question is closed."
They actually tested the hypothesis repeatedly.
Researchers looked at:
- MMR vaccination and autism
- vaccination timing
- autism regression
- thimerosal exposure
- cumulative vaccine exposure
- different vaccine schedules
- different countries
- children with and without developmental risk factors
And the MMR-autism association repeatedly failed to appear in well-designed epidemiological studies.
For example, a large Danish study published in 2002 compared children who received MMR with those who had not and found no increased risk of autism or autistic disorder associated with MMR vaccination.
Other large studies subsequently produced similar findings.
The Institute of Medicine's 2004 review concluded that the epidemiological evidence favored rejection of a causal relationship between MMR vaccine and autism. CDC summarizes that conclusion and the subsequent evidence.
5. Then the argument moved to mercury
And this is where the story gets really interesting.
In the late 1990s, attention shifted from:
MMR → autism
to:
Thimerosal → autism
Thimerosal is an ethylmercury-containing preservative that had been used in some vaccines, particularly multidose vaccine vials.
The argument went something like:
Autism diagnoses increasing
childhood vaccines increasing
some vaccines contain mercury
=
mercury exposure may be causing autism.
This was a more biologically plausible hypothesis than the simple "MMR causes autism" argument, because mercury is unquestionably biologically active and can be toxic at sufficiently high exposures.
So researchers investigated it.
6. The really interesting natural experiment
The United States reduced and essentially eliminated thimerosal from routine childhood vaccines beginning around 1999–2001.
That created something close to a natural experiment.
If thimerosal were causing a substantial fraction of autism, you'd expect autism rates to subsequently decline as exposure declined.
They didn't.
Autism diagnoses continued increasing.
Similar observations occurred in Denmark and Sweden, where thimerosal-containing vaccines were removed from childhood vaccination programs in the early 1990s while autism diagnoses continued to rise.
CDC summarizes several of these studies and the history of thimerosal reduction/removal.
That doesn't by itself prove that mercury can never contribute to any neurological condition. It does, however, make "thimerosal in childhood vaccines is causing the autism increase" very difficult to reconcile with the population data.
7. The hypothesis then expanded again
Once MMR and thimerosal became difficult to support, the claim evolved.
Instead of:
MMR causes autism
or
Mercury causes autism
you began seeing:
The entire vaccine schedule causes autism.
This is a substantially broader hypothesis.
It can include:
- number of vaccines
- number of antigens
- aluminum adjuvants
- immune stimulation
- vaccine combinations
- timing of vaccination
- cumulative exposure
- interactions between ingredients
- genetically susceptible children
This is the version of the argument that is still commonly encountered today.
And it creates a methodological problem:
You have to specify exactly what exposure you're claiming causes autism.
Otherwise almost any epidemiological result can be interpreted to support the hypothesis.
8. Researchers tested "too many vaccines"
This was also investigated.
If the number of vaccines or antigens received during infancy caused autism, you'd expect children receiving greater exposure to have higher autism rates.
Large studies haven't demonstrated that pattern.
One particularly useful example is a study published in Pediatrics in 2013 examining cumulative antigen exposure during the first two years of life. It found no association between cumulative antigen exposure and autism spectrum disorder.
That's important because it directly addresses a version of the modern argument:
"Maybe it's not one vaccine; maybe it's the total immune burden."
9. Meanwhile, something else was happening: autism diagnosis was changing
This is an absolutely crucial part of the history.
The increase in autism diagnoses wasn't simply:
same disorder + same diagnostic criteria + more children developing it.
The definition of autism changed considerably.
For example, DSM-III (1980) introduced infantile autism as a distinct diagnosis.
DSM-IV (1994) subsequently included a much broader spectrum of pervasive developmental disorders, including:
- autistic disorder
- Asperger's disorder
- pervasive developmental disorder-not otherwise specified
And over the decades:
- screening improved,
- awareness increased,
- schools became better at identifying developmental disabilities,
- clinicians became better at recognizing autism,
- diagnostic boundaries broadened,
- children who previously received other diagnoses could receive an autism diagnosis.
So the raw increase in diagnoses isn't equivalent to an equivalent increase in the underlying biological incidence.
That doesn't mean every increase is explained by diagnostic changes. Researchers continue to investigate why autism prevalence has changed.
But it makes:
"Autism increased after vaccines increased, therefore vaccines caused the increase"
a very weak inference.
10. Genetics changed the picture dramatically
Another major development occurred as autism genetics advanced.
Researchers discovered that autism has a substantial genetic component, involving many genes and many different genetic mechanisms.
There isn't an "autism gene."
Instead, there are hundreds of genetic variants that can contribute to susceptibility, along with environmental/developmental influences.
This helped move autism research away from looking for a single environmental culprit and toward a complex neurodevelopmental model.
That doesn't logically prove that no environmental factor could ever influence autism. But it provides a much better-supported framework for understanding why autism is so heterogeneous.
11. By the 2000s–2010s, the evidence against MMR and thimerosal became enormous
This is where the claim really changed.
The original question:
"Could MMR cause autism?"
became:
"Could some particular component, dose, timing, combination, or susceptible subgroup explain autism?"
Researchers kept testing those possibilities.
A major 2014 meta-analysis pooled data from over 1.25 million children and found no association between vaccination and autism/ASD, including analyses of:
- MMR
- thimerosal/mercury
- mercury exposure
- vaccination status
The authors concluded that the evidence did not support an association between vaccination and autism.
12. What about studies that do find an association?
This is important because you will encounter them.
There have been studies reporting associations between vaccines and autism-related outcomes.
That doesn't mean they should simply be ignored.
Instead, scientists ask:
- Was the study randomized?
- Was there an appropriate control?
- Was exposure measured accurately?
- Was autism diagnosed consistently?
- Was the sample representative?
- Were confounding variables controlled?
- Was the result replicated?
- Is there a plausible biological mechanism?
- Does it agree with the larger body of evidence?
This is why one study isn't enough to overturn a large body of evidence.
And this is something I think you've been getting at throughout our vaccine discussions: you don't want "the government says no" as the argument. You want to know what the actual studies did.
That's the right question.
13. And now we have a very strange historical reversal
This brings us to 2025–2026.
The scientific evidence didn't suddenly change.
The U.S. government's public messaging changed.
In November 2025, CDC altered its autism/vaccine webpage to say that the statement "vaccines do not cause autism" was not an evidence-based claim because studies had not ruled out the possibility of infant vaccines contributing to autism. CDC's page now presents a much more skeptical interpretation of the evidence.
This represents a major departure from decades of CDC messaging, and it has been controversial.
At the same time, the current administration has emphasized additional research into possible environmental contributors to autism.
And as of August 2026, the issue remains politically active; recent federal policy discussions have included changes to childhood vaccination recommendations and renewed claims about MMR and autism.
But here's the key distinction:
A change in what a government agency says is not the same thing as a change in the underlying scientific evidence.
The evidence accumulated since 1998 doesn't disappear because the CDC changes its webpage.
So the evolution of the claim looks roughly like this
1940s–1980s
Autism recognized as a neurodevelopmental condition.
↓
1990s
Autism diagnoses rise dramatically.
↓
1998
Wakefield publishes the 12-child MMR paper.
↓
1998–2000s
"MMR causes autism."
↓
1999–2001
Attention shifts toward thimerosal/mercury.
↓
2000s
"Mercury in vaccines causes autism."
↓
2000s–2010s
Studies repeatedly fail to support MMR or thimerosal hypotheses.
↓
2010
Wakefield's paper fully retracted; GMC finds serious professional misconduct.
↓
2010s
Argument broadens:
"Maybe it's the whole vaccine schedule."
↓
2010s–2020s
Researchers investigate:
- total antigen exposure
- aluminum
- timing
- genetic susceptibility
- immune activation
- vaccine combinations
↓
Current argument
"The existing studies haven't ruled out a susceptible subgroup or particular vaccine exposure."
And that last version is considerably harder to test than the original claim because it can become extremely specific:
"Maybe vaccines cause autism in genetically susceptible children when given at a particular developmental window."
That's a legitimate hypothesis to investigate, but it isn't the same as having evidence that the hypothesis is true.
One thing I would emphasize
There is a huge difference between these three statements:
A. "Vaccines cause autism."
B. "We have not proven that vaccines can never contribute to autism in any conceivable circumstance."
C. "There is currently good evidence that vaccines cause autism."
Those are three very different propositions.
The evidence accumulated since 1998 is very strong against A, particularly for MMR and thimerosal. The evidence cannot logically establish an absolute metaphysical "zero possibility" for every conceivable vaccine, every dose, every individual, and every mechanism—which is why B is technically much easier to defend.
But B does not provide evidence for C.
And that's an important distinction in the debate.
One especially useful source for you
The National Academies' history of the Wakefield episode is worth reading because it isn't simply a CDC fact sheet; it discusses how the original paper, the later investigation, the coauthors' partial retraction, and the eventual Lancet retraction fit together.
National Academies — Fostering Integrity in Research, discussion of the Wakefield case
If you want to go one step deeper, the next thing I'd suggest is that we take the actual major autism/vaccine studies in chronological order—Wakefield → Danish MMR study → thimerosal studies → IOM reviews → large meta-analyses—and look at what each one actually found and what its limitations were. That would let us separate the genuinely weak studies from the very strong ones rather than treating "science says no" as one giant blob.
How about the idea that these vaccines cause swelling in the brain and then that causes a lot of these chronic conditions in children...
Yes — there is a real biological concept behind that claim, but the leap from "vaccines can activate inflammation" to "vaccines cause brain swelling that produces chronic conditions such as autism" is much bigger than it sounds.
I'd separate the claim into several pieces.
1. Can vaccines cause inflammation?
Yes. That's not controversial.
Vaccination deliberately activates the immune system. Fever, soreness, fatigue, and transient inflammatory responses are expected consequences of that immune activation.
But systemic immune activation isn't the same thing as encephalitis (inflammation of the brain).
2. Can a vaccine ever cause a serious neurological inflammatory reaction?
Very rarely, yes.
There are documented neurological adverse events following some vaccines, and vaccine safety reviews have specifically investigated conditions such as encephalitis, encephalopathy, seizures, and acute disseminated encephalomyelitis (ADEM). For some vaccine/adverse-event combinations, evidence has supported causality; for others, the evidence has been insufficient or has not shown an association.
That's important because I don't think we should make the opposite mistake and say "vaccines can never cause neurological problems." They can, just very rarely.
3. Is there evidence that routine childhood vaccination causes chronic brain inflammation?
This is where the evidence becomes much weaker.
There is research finding evidence of altered immune signaling and neuroinflammation in some people with autism. For example, systematic reviews of postmortem brain studies have found differences involving microglia and inflammatory signaling.
But that establishes:
Autism ↔ evidence of neuroimmune/inflammatory abnormalities
It does not establish:
Vaccination → brain inflammation → autism
That's a critical distinction.
In fact, current research into autism's immune biology is much broader than vaccines. Researchers are investigating genetics, prenatal immune activation, immune signaling, microglia, maternal health, and many other mechanisms. Recent reviews still describe the exact causal pathways as unresolved.
There's also a problem with the word "swelling"
When someone says:
"Vaccines cause swelling in the brain."
I would immediately ask:
What exactly do they mean by swelling?
There are several very different things that can get lumped together:
- temporary activation of immune cells,
- inflammatory cytokines,
- activation of microglia,
- blood-brain-barrier changes,
- cerebral edema,
- encephalitis,
- encephalopathy.
Those are not interchangeable.
Actual cerebral edema is a serious medical condition. It isn't something we'd expect to quietly occur in large numbers of vaccinated children and then manifest years later as autism.
And here's a particularly important test of the hypothesis
If the proposed mechanism is:
vaccination → brain inflammation → autism/chronic neurological disease
we should be able to find evidence of that sequence.
We would want to see things like:
- Vaccinated children developing measurable neurological inflammation more frequently than appropriate controls.
- That inflammation occurring before the neurological condition.
- A dose/timing relationship.
- Higher risk with greater inflammatory response.
- A reproducible biological mechanism.
- The effect showing up in large epidemiological studies.
That chain hasn't been demonstrated for autism.
A major National Academies review specifically examined both epidemiological evidence and proposed biological mechanisms for MMR and thimerosal. It concluded that the epidemiological evidence favored rejecting a causal relationship and that proposed biological mechanisms for vaccine-induced autism were theoretical.
And a 2014 meta-analysis encompassing over 1.25 million children in cohort studies found no association between vaccination and autism, including analyses of MMR, thimerosal, and mercury.
One wrinkle worth keeping in our investigation
You'll notice that the current CDC position is now more nuanced than its older blanket statement. The CDC's 2025 page says that studies have not completely ruled out the possibility that infant vaccines contribute to autism and that HHS is investigating potential biological mechanisms, including neuroinflammation.
That doesn't mean CDC has demonstrated that vaccines cause neuroinflammation leading to autism. It means the agency is saying some questions haven't been completely resolved and is supporting additional investigation.
That's actually a useful distinction for the way we've been approaching this:
"A mechanism is biologically conceivable" ≠ "the mechanism occurs in vaccinated children" ≠ "the mechanism causes autism."
And I'd be very interested in following the neuroinflammation hypothesis itself next, because that's where this claim becomes testable rather than just rhetorical. We can look at what researchers actually mean by neuroinflammation, how they measure it in children, and whether there is evidence connecting vaccination to it.
There's a lot of people online that talk about how their children act before they get their vaccines compared to how they act after they get their vaccines. There's a lot of people saying that their kids change their behavior noticeably after vaccine's. Has there been any studies or research about that?
Yes. Researchers have specifically studied the phenomenon you're describing: parents noticing a change in behavior or development after a vaccination, including apparent regression.
And I think this is an important question because we shouldn't dismiss the observation itself. A parent saying, "My child was doing X, then after the vaccination I noticed Y" is reporting a real observation. The scientific question is whether the vaccine caused the change, whether the timing was coincidental, or whether something else explains the pattern.
Researchers have looked at the timing directly
One of the earliest major studies after the MMR controversy examined when parents first noticed developmental concerns and when regression occurred relative to MMR vaccination.
A 1999 Lancet study examined 498 children with autism and specifically looked for clustering of:
- autism diagnosis,
- first parental concern,
- and developmental regression
after MMR vaccination.
They did not find clustering of autism or regression following vaccination.
That's a pretty direct test of the question:
"Do children disproportionately begin showing these changes shortly after vaccination?"
The answer in that study was no.
Another study looked specifically at regression
A 2002 population study examined 473 children with autism and looked at developmental regression and gastrointestinal problems in relation to MMR vaccination.
About 25% had developmental regression, but the proportion did not increase after MMR was introduced, and regression wasn't more common among children who had received MMR before their parents became concerned about development.
Interestingly, the researchers found something relevant to your question: parental descriptions of when symptoms began sometimes changed over time.
In 13 cases, earlier medical records contained concerns that began before MMR, while later parental histories described symptoms as beginning after MMR. The researchers specifically identified this as a potential recall/reporting bias.
That doesn't mean parents were lying. Memory is surprisingly malleable, particularly when someone subsequently learns about a possible explanation for a frightening event.
But here's an even more interesting study design
Researchers have also used self-controlled case-series methods.
Instead of comparing:
vaccinated children vs. unvaccinated children
they compare the same child before and after vaccination.
That's useful because the child serves as their own control, eliminating many differences between families.
Researchers have examined periods such as:
before vaccination → vaccination → 2 months → 4 months → 6 months
and asked whether autism regression, parental concern, or diagnosis occurs unusually frequently after vaccination.
These analyses generally have not found temporal clustering of regression following MMR.
There was an interesting exception: one analysis found a statistical clustering of parental concern within six months of vaccination. But the investigators concluded that this appeared to be an artifact associated with the difficulty of determining precisely when developmental symptoms began and the fact that both vaccination and recognition of developmental problems tend to occur around the same ages.
That's actually a really good example of why this question is harder than it initially appears.
And there's newer evidence too
A 2016 study looked at 2,755 children with autism, specifically comparing children with different patterns of onset:
- early onset,
- plateau,
- delay/regression,
- regression.
If vaccines were triggering a distinctive form of regressive autism, you'd expect the children with regression to have a noticeably different vaccination history.
They didn't.
The vaccination rates were essentially equivalent across the different autism-onset groups.
And there's a very recent 2026 study using electronic health records from approximately 2.5 million U.S. children examining the relationship between first MMR vaccination before age two and childhood autism. It's specifically designed to address some of the biases that can affect vaccine-timing studies.
But I want to make an important distinction
These studies do not establish that no child has ever experienced a genuine behavioral change after vaccination.
That's a much stronger claim.
They address the population-level question:
Does vaccination cause a reproducible increase in developmental regression or autism-like behavioral change?
And the evidence so far says no convincing population-level effect has been demonstrated.
That's different from:
"A parent couldn't possibly have observed a real change."
A child can absolutely have a real change in behavior after a vaccination.
The question is what caused it.
There's actually a really interesting phenomenon here
The timing of routine childhood vaccines overlaps with a period when many developmental differences naturally become much more obvious.
For example, MMR is typically given around 12–15 months, while autism-related developmental differences can become increasingly apparent around the same period.
So you have:
Vaccination
↓
12–18 months of age
↓
Parents increasingly notice language/social differences
That creates a very compelling temporal association even if the two events aren't causally related.
And that is precisely why researchers have gone beyond asking "Did the parent notice a change after vaccination?"
They've asked:
"Does this happen more often than we would expect by chance?"
That's the much harder question.
One thing I'd like to explore next
Given the direction we've been taking this conversation, I think there's a particularly interesting experiment for us to examine:
Studies where parents kept prospective developmental records rather than relying on memories after the child was diagnosed.
That's potentially much closer to the question you're asking because we could look at:
What was the child's documented behavior immediately before vaccination → what happened afterward → how long did it last → was there actual developmental regression → and did the same pattern occur in unvaccinated children?
That gets us away from simply saying "research says vaccines don't cause autism" and lets us examine the actual before-and-after phenomenon that parents are describing.
Vaccine hesitancy is increasing. Taking previous years data and what scientists already know about infectious disease, make a prediction or best estimate of how that's going to affect disease in our society of the United States if say the vaccination rate drops below 80%. Can you do that?
Yes. We can make a reasoned projection, and I think it would actually be useful to do it disease-by-disease rather than simply saying "vaccination goes down → disease goes up."
One important clarification first:
There is no single vaccination percentage at which every vaccine-preventable disease suddenly returns.
The critical threshold depends on the disease's contagiousness, vaccine effectiveness, existing immunity, and—very importantly—whether the remaining unvaccinated people are randomly distributed or concentrated in communities.
That last point is huge.
We're already seeing the beginning of this
U.S. kindergarten MMR coverage was about 96% in 2018–19, fell to 92.7% in 2023–24, and was about 92.5% in 2024–25. The latest 2025–26 data show another small decline, to roughly 92.4%, while exemptions reached a record 4.2%.
And we've already seen the epidemiological consequence: measles outbreaks have increased substantially. In 2025, the U.S. had 800 reported cases by April 17 alone, with 96% occurring in people who were unvaccinated or whose vaccination status was unknown.
So we're not entirely predicting from theory—we're watching the early part of the process happen.
Let's imagine 80%
Suppose childhood vaccination coverage eventually falls from roughly 92–93% nationally to 80%.
For a rough mental model, that's:
100 children
→ 80 vaccinated
→ 20 susceptible
instead of:
100 children
→ 92 vaccinated
→ 8 susceptible
That's a 2.5-fold increase in the susceptible population.
But the consequences wouldn't be evenly distributed.
If those 20 susceptible children are scattered among vaccinated children, transmission may still be limited.
If they're clustered together:
20 susceptible children can become a very large problem.
That's because infectious diseases don't care about the national average.
🦠 Measles would probably be the first major warning sign
Measles is extraordinarily contagious.
The approximate population immunity threshold is around 95%, which is why the CDC specifically identifies >95% coverage as necessary for maintaining community protection against measles.
At 80% coverage, we'd have an enormous gap.
I'd expect:
Short term
- More imported cases producing outbreaks
- More outbreaks lasting longer
- More geographic spread
- More schools experiencing outbreaks
- More post-exposure quarantine
- More infants and immunocompromised people exposed
Medium term
Measles would begin moving from:
"an occasional imported outbreak"
toward:
"a recurring endemic disease."
That's a major change.
The United States eliminated endemic measles transmission in 2000. The CDC is already attributing increasing measles activity partly to declining vaccination coverage.
At 80%, I would expect elimination to be lost in many regions, particularly where vaccination rates were substantially below the national average.
🫁 Pertussis would probably increase too
Pertussis is different from measles because immunity isn't as absolute or lifelong.
Even vaccinated people can occasionally become infected.
But vaccination substantially reduces severe disease, particularly in infants.
At 80% coverage I'd expect:
- more childhood infections,
- more transmission to infants,
- more hospitalizations,
- more infant deaths,
- larger cyclical outbreaks.
And because infants are too young to have completed the vaccination series, they're particularly dependent on everyone around them having immunity.
🧠 Polio is a particularly interesting case
Polio is where I'd expect the consequences to be delayed.
The U.S. has eliminated endemic poliovirus transmission.
But that's not because the virus disappeared from Earth.
It's because transmission has been interrupted through vaccination.
At 80% coverage, I would not expect an immediate explosion of polio.
Instead, you'd have:
Imported poliovirus
↓
infects an undervaccinated community
↓
silent transmission
↓
eventual paralytic case
The terrifying thing about polio is that most infections don't cause paralysis.
So you can have transmission occurring without realizing it.
We actually saw a warning of this in New York in 2022, when a paralytic polio case was identified and wastewater surveillance subsequently detected poliovirus circulation.
So polio would be a low-frequency but potentially catastrophic consequence of declining immunity.
🐔 Chickenpox
Varicella would probably increase substantially.
Unlike measles, the disease is usually less dangerous, but complications can include:
- pneumonia
- bacterial skin infections
- encephalitis
- hospitalization
- death
And there's an additional issue we've discussed before:
more circulating varicella virus means more people infected and therefore more opportunities for later shingles.
The relationship is complicated, though, so I wouldn't claim that a decline in childhood vaccination automatically produces a proportional increase in shingles.
🧫 Hib and pneumococcus
These are particularly important because the vaccines prevent a lot of severe disease in young children.
At lower coverage we'd expect more:
- meningitis
- bloodstream infections
- pneumonia
- severe ear infections
And this is where the consequences become somewhat less visible than measles.
You might not get a dramatic national outbreak.
Instead you'd get:
hundreds or thousands of additional serious infections distributed across the population.
💀 What about deaths?
This is where I'd be very careful about giving you a fake-precise number.
We can model deaths, but we'd need to specify:
- which vaccines are declining,
- how quickly coverage falls,
- which age groups are affected,
- whether immunity in adults is maintained,
- geographic clustering,
- healthcare access,
- disease importation,
- vaccine effectiveness,
- and whether vaccination eventually rebounds.
A statement such as:
"80% vaccination would cause X deaths per year."
would be unjustifiably precise.
But the direction is much more predictable.
My best qualitative projection would be:
| Coverage | Likely U.S. situation |
|---|---|
| 95%+ | Strong protection against highly contagious diseases such as measles |
| 90–95% | Increasing outbreaks, especially in undervaccinated pockets |
| ~85% | Sustained outbreaks become increasingly likely |
| ~80% | Multiple vaccine-preventable diseases begin producing substantially more illness; measles elimination becomes very difficult/impossible to maintain |
| <80% | Increasing risk of sustained transmission and re-establishment of diseases previously eliminated |
Those aren't hard thresholds, particularly below 95%. They're a conceptual projection.
The part I think is most important
The national number 80% actually understates the danger if vaccination becomes geographically concentrated.
Imagine two communities:
Community A
95 vaccinated
5 unvaccinated
Community B
65 vaccinated
35 unvaccinated
National average:
80%
Community A may remain relatively well protected.
Community B is a tinderbox.
That's exactly why the CDC emphasizes that pockets of low vaccination can exist even when national coverage is relatively high.
And we've already seen this phenomenon in the current measles outbreaks: large outbreaks have disproportionately occurred in close-knit communities with low vaccination coverage rather than being evenly distributed across the country.
So my best estimate?
If U.S. childhood vaccination coverage genuinely fell to ~80% and stayed there, I would expect:
Within a few years:
- measles outbreaks become common rather than unusual;
- some areas experience sustained measles transmission;
- pertussis and varicella increase;
- outbreaks of other vaccine-preventable diseases become more frequent;
- schools and healthcare systems experience substantially more disruption.
Over a longer period:
- measles could become endemic again;
- polio would become a credible reintroduction threat;
- severe childhood infections and deaths would increase;
- diseases currently controlled primarily through vaccination would begin behaving more like they did before widespread immunization.
And importantly, this isn't an argument that "every unvaccinated child will get sick." Most won't. The population-level effect comes from increasing the number of opportunities for transmission until eventually the pathogen finds enough susceptible people to maintain itself.
That's the fascinating thing about infectious disease epidemiology: the individual risk and the population risk aren't the same thing.
If you'd like, we can take this one step further and actually build a hypothetical 80% U.S. vaccination scenario using historical pre-vaccine disease rates and modern U.S. population numbers to estimate roughly how many additional cases, hospitalizations, and deaths we might expect for measles, pertussis, polio, Hib, pneumococcal disease, and chickenpox. That would give you something much more concrete than a qualitative prediction.
Absolutely. Since we've covered a very wide range of subjects—virology, viral detection/sequencing, vaccine development and history, vaccine trials/placebos, vaccine safety, autism claims, mRNA vaccines, viral spillover, laboratory biosafety, smallpox/Ebola research, and vaccine hesitancy—I think the most useful thing is to give you a source list organized by topic, rather than one enormous unstructured list.
One caveat: some of our earlier answers were based on general scientific knowledge rather than a specific webpage, so this is the collection of the sources I actually drew on or pointed you toward, plus the primary/authoritative resources that underpin those discussions. I've also included the websites as plain text, as you requested.
1. Viruses — What They Are, How We Detect Them, Image Them, and Sequence Them
CDC — About Viruses
Website:
https://www.cdc.gov/viral-vectors/about/index.html
Useful for basic virus biology and terminology.
NIAID — Understanding Viruses
Website:
https://www.niaid.nih.gov/diseases-conditions/understanding-viruses
Basic explanation of viruses, infection, replication, and host interaction.
NIH/NIAID — Virus Research
Website:
https://www.niaid.nih.gov/research/virus-research
Broad overview of how researchers study viruses.
National Human Genome Research Institute — DNA Sequencing
Website:
https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Fact-Sheet
Good introduction to how genetic sequences are determined.
NCBI — National Center for Biotechnology Information
Website:
https://www.ncbi.nlm.nih.gov/
One of the most important resources we've discussed indirectly. NCBI contains enormous databases of viral genomes, publications, protein sequences, and sequence-analysis tools.
NCBI Virus
Website:
https://www.ncbi.nlm.nih.gov/labs/virus/
Useful for actually exploring viral genome sequences.
2. Vaccines — Types and How They Work
CDC — Different Types of Vaccines
Website:
https://www.cdc.gov/vaccines/basics/types/index.html
Covers:
- live attenuated
- inactivated
- subunit
- toxoid
- conjugate
- mRNA
- viral-vector vaccines
WHO — Vaccines and Immunization
Website:
https://www.who.int/health-topics/vaccines-and-immunization
Broad overview of vaccine technology and immunization.
NIAID — Vaccine Research
Website:
https://www.niaid.nih.gov/research/vaccine-research
Good for understanding how vaccines are developed and studied.
FDA — Vaccine Development 101
Particularly useful for the clinical-development process.
3. How New Vaccines Are Tested
This became a major part of our discussion.
FDA — Vaccine Development 101
Explains:
- preclinical testing
- Phase 1
- Phase 2
- Phase 3
- licensure
- post-licensure monitoring
FDA — Clinical Trial Design Guidance
This was particularly relevant to our discussion of placebo-controlled trials.
WHO — Guidelines on Clinical Evaluation of Vaccines
Website:
https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9
This is one of the best resources for your placebo/control question.
It explicitly discusses:
- placebo controls
- unrelated vaccine controls
- active controls
- existing vaccines as comparators
- combination-vaccine controls
The WHO document states that the control may be a vaccine for another disease or an existing vaccine against the same disease.
4. Childhood Vaccine Schedule
CDC — Child and Adolescent Immunization Schedule
Website:
https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html
This is the current CDC schedule we discussed.
CDC — Child Immunization Schedule Notes
Website:
https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-notes.html
Useful for understanding the exceptions, catch-up schedules, contraindications, and special circumstances.
CDC — Immunization Schedule by Medical Indication
Website:
https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-medical-indication.html
5. Placebo-Controlled Vaccine Trials
This was one of your major questions.
WHO — Clinical Evaluation of Vaccines
Website:
https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9
Again, this is probably the single most useful document for understanding why one vaccine might use saline placebo while another uses an active vaccine comparator.
FDA — Vaccine Clinical Trials
National Academies — Vaccine Safety
Useful for understanding how evidence for vaccine adverse events is evaluated.
6. History of Vaccines
History of Vaccines — College of Physicians of Philadelphia
Website:
https://historyofvaccines.org/
This is an excellent historical resource.
It covers:
- variolation
- Edward Jenner
- smallpox vaccination
- early vaccine development
- vaccine controversies
- development of modern vaccines
WHO — Smallpox
Website:
https://www.who.int/emergencies/situations/smallpox
Useful for the history of eradication.
CDC — History of Smallpox
Website:
https://www.cdc.gov/smallpox/about/index.html
7. Vaccine Failures, Mistakes, and Historical Problems
CDC — Vaccine Safety
Website:
https://www.cdc.gov/vaccine-safety/
General resource for adverse events and historical vaccine safety issues.
FDA — Vaccine Safety
Website:
https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics
National Academies — Adverse Effects of Vaccines
This is particularly useful because it examines causality, rather than simply listing adverse events.
8. mRNA Vaccine Technology
NIH/NIAID — mRNA Vaccine Research
Website:
https://www.niaid.nih.gov/diseases-conditions/mrna-vaccines
CDC — Understanding mRNA COVID-19 Vaccines
Website:
https://www.cdc.gov/covid/vaccines/how-they-work.html
FDA — COVID-19 Vaccines
Nature — The Long History of mRNA Vaccines
Website:
https://www.nature.com/articles/d41586-021-02483-w
This is particularly useful for the question we discussed about whether mRNA technology was suddenly invented in 2020.
9. Can mRNA Change Your DNA?
CDC — Understanding mRNA Vaccines
Website:
https://www.cdc.gov/covid/vaccines/how-they-work.html
NIH — mRNA Vaccine Technology
Website:
https://www.niaid.nih.gov/diseases-conditions/mrna-vaccines
National Human Genome Research Institute
Website:
https://www.genome.gov/
Good background for understanding DNA, RNA, transcription, and genome biology.
Nature — mRNA Vaccine Biology
Website:
https://www.nature.com/collections/hggrhjsjdd
Nature's collection of research and explanations concerning mRNA vaccine technology.
10. Viral DNA in the Human Genome
This came up when we discussed the fact that a significant fraction of the human genome has viral origins.
National Human Genome Research Institute
Website:
https://www.genome.gov/
NCBI Bookshelf — Endogenous Retroviruses
Website:
https://www.ncbi.nlm.nih.gov/books/
Nature — Human Genome and Endogenous Retroviruses
Website:
https://www.nature.com/
Smithsonian / Human Origins
Website:
https://humanorigins.si.edu/
The key scientific concept here is endogenous retroviruses—ancient viral genetic material that became integrated into ancestral genomes.
11. Viral Spillover — Animals → Humans
CDC — One Health
Website:
https://www.cdc.gov/one-health/
WHO — Zoonoses
Website:
https://www.who.int/news-room/fact-sheets/detail/zoonoses
NIH/NIAID — Emerging Infectious Diseases
Website:
https://www.niaid.nih.gov/research/emerging-infectious-diseases
UNEP — Preventing the Next Pandemic
This is useful for understanding why animal contact doesn't automatically produce a human pandemic.
12. SARS-CoV-2 Origins
WHO — Origins of SARS-CoV-2
Website:
https://www.who.int/activities/tracking-SARS-CoV-2-variants
WHO — Scientific Advisory Group for the Origins of Novel Pathogens
Website:
https://www.who.int/groups/scientific-advisory-group-on-the-origins-of-novel-pathogens
Nature — SARS-CoV-2 Origins
Website:
https://www.nature.com/articles/s41591-021-01203-y
Cell — The Proximal Origin of SARS-CoV-2
Website:
https://www.cell.com/cell/fulltext/S0092-8674(20)30246-9
This is one of the key papers in the natural-origin discussion.
13. Laboratory Biosafety and Biosecurity
This was another major thread of our discussion.
WHO — Laboratory Biosafety Manual
Website:
https://www.who.int/publications/i/item/9789240011311
One of the major international biosafety references.
WHO — Laboratory Biosecurity Guidance
Website:
https://www.who.int/publications/i/item/9789240095113
Useful for the distinction between biosafety and biosecurity.
CDC/NIH — Biosafety in Microbiological and Biomedical Laboratories (BMBL)
Website:
https://www.cdc.gov/labs/bmbl/index.html
This is one of the principal U.S. biosafety references.
14. Gain-of-Function Research
National Science Advisory Board for Biosecurity
Website:
https://osp.od.nih.gov/biotechnology/national-science-advisory-board-for-biosecurity/
National Academies — Gain-of-Function Research
Website:
https://www.nationalacademies.org/
U.S. Government Policy for Oversight of High-Consequence Pathogen Research
Website:
https://www.whitehouse.gov/
NIH — High-Risk Research Policies
Website:
https://osp.od.nih.gov/
This is a particularly complicated subject because "gain of function" is used much more broadly in casual discussion than it is in many formal policy contexts.
15. Ebola Research
NIAID — Ebola
Website:
https://www.niaid.nih.gov/diseases-conditions/ebola
CDC — Ebola
Website:
https://www.cdc.gov/ebola/
WHO — Ebola
Website:
https://www.who.int/health-topics/ebola
NIAID — Ebola Treatment Research
Website:
https://www.niaid.nih.gov/diseases-conditions/ebola-treatment
16. Smallpox Research
WHO — Smallpox
Website:
https://www.who.int/emergencies/situations/smallpox
WHO — Research Using Live Variola Virus
Website:
https://www.who.int/activities/research-using-live-variola-virus
WHO — Advisory Committee on Variola Virus Research
Website:
https://www.who.int/groups/who-advisory-committee-on-variola-virus-research
WHO — Variola Repository Inspections
Website:
https://www.who.int/activities/variola-virus-repository-safety-inspections
This became particularly relevant to our discussion of whether the benefits of retaining live smallpox justify the risks.
And there is a very recent 2026 WHO inspection report concerning the CDC's variola repository in Atlanta:
https://www.who.int/publications/i/item/B09763
The WHO report describes the April–May 2026 biosafety/biosecurity inspection.
17. Vaccine–Autism History
This is probably the section I'd recommend spending the most time with if you're continuing your investigation.
The Lancet — Original Wakefield Paper
Historical citation:
Wakefield et al., 1998, The Lancet.
Website:
https://www.thelancet.com/
Important: The paper was subsequently retracted.
The Lancet — Retraction
Website:
https://www.thelancet.com/
British Medical Journal — Wakefield Investigation
Website:
https://www.bmj.com/
National Academies — Vaccine Safety / Wakefield Discussion
Website:
https://www.nationalacademies.org/
This was one of the sources we used when discussing the history of the Wakefield episode.
18. MMR and Autism
CDC — MMR Vaccine Safety
Website:
https://www.cdc.gov/vaccine-safety/vaccines/mmr.html
This discusses the MMR/autism question and summarizes the safety evidence.
CDC — Measles Vaccination
Website:
https://www.cdc.gov/measles/vaccines/
Also discusses MMR effectiveness and the autism claim.
PubMed
Website:
https://pubmed.ncbi.nlm.nih.gov/
This is where you can find the individual MMR/autism studies.
19. Thimerosal / Mercury and Autism
CDC — Thimerosal and Vaccines
Website:
https://www.cdc.gov/vaccine-safety/about/thimerosal.html
This is one of the most useful current CDC pages for this particular claim. It documents the removal of thimerosal from routine childhood vaccines and summarizes the research.
FDA — Thimerosal
Website:
https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/thimerosal-and-vaccines
National Academies — Immunization Safety Review
Website:
https://www.nationalacademies.org/
PubMed
Website:
https://pubmed.ncbi.nlm.nih.gov/
20. Autism and Developmental Regression
PubMed
Website:
https://pubmed.ncbi.nlm.nih.gov/
This is the best place to search for the individual studies we discussed.
Useful search terms:
MMR autism regression
vaccination developmental regression autism
MMR temporal association autism
vaccines autism prospective study
NCBI Bookshelf
Website:
https://www.ncbi.nlm.nih.gov/books/
21. Neuroinflammation and Autism
PubMed
Website:
https://pubmed.ncbi.nlm.nih.gov/
Search:
autism neuroinflammation
autism microglia
autism immune activation
autism neuroimmune
National Institute of Mental Health
Website:
https://www.nimh.nih.gov/
NIH
Website:
https://www.nih.gov/
These are useful for separating the legitimate finding that immune/neuroinflammatory processes are being investigated in autism from the much stronger claim that vaccines cause chronic brain inflammation leading to autism.
22. Vaccine Side Effects and Neurological Events
CDC — Vaccine Safety
Website:
https://www.cdc.gov/vaccine-safety/
CDC — MMWR
Website:
https://www.cdc.gov/mmwr/
Vaccine Adverse Event Reporting System
Website:
https://vaers.hhs.gov/
Vaccine Safety Datalink
Website:
https://www.cdc.gov/vaccine-safety-systems/vsd/
These are particularly important because VAERS alone cannot establish causality. The Vaccine Safety Datalink and other active-surveillance systems are designed to investigate signals more rigorously.
23. Vaccine Hesitancy
WHO — Vaccine Hesitancy
CDC — Vaccine Confidence
Website:
https://www.cdc.gov/vaccines/parents/why-vaccinate/vaccine-decision.html
Kaiser Family Foundation / KFF
Website:
https://www.kff.org/
Useful for polling and public attitudes toward vaccination.
24. Declining Vaccination and Disease Outbreaks
CDC — Measles Data
Website:
https://www.cdc.gov/measles/data-research/
CDC — Measles Vaccination
Website:
https://www.cdc.gov/measles/vaccines/
CDC — MMWR
Website:
https://www.cdc.gov/mmwr/
These are particularly useful for tracking the relationship between vaccination coverage and measles outbreaks.
WHO — Measles
Website:
https://www.who.int/health-topics/measles
25. Polio
CDC — Polio
Website:
https://www.cdc.gov/polio/
WHO — Polio
Website:
https://www.who.int/health-topics/poliomyelitis
Global Polio Eradication Initiative
Website:
https://polioeradication.org/
26. Pertussis
CDC — Pertussis
Website:
https://www.cdc.gov/pertussis/
WHO — Pertussis
Website:
https://www.who.int/health-topics/pertussis
27. Chickenpox / Varicella
CDC — Chickenpox
Website:
https://www.cdc.gov/chickenpox/
CDC — Varicella Vaccination
Website:
https://www.cdc.gov/chickenpox/vaccines/
28. Hib
CDC — Hib Disease
Website:
https://www.cdc.gov/hi-disease/
CDC — Hib Vaccination
Website:
https://www.cdc.gov/hi-disease/vaccines/
29. Pneumococcal Disease
CDC — Pneumococcal Disease
Website:
https://www.cdc.gov/pneumococcal/
WHO — Pneumococcal Disease
Website:
https://www.who.int/health-topics/pneumococcal-disease
30. Vaccine Effectiveness / Population Immunity
CDC — Vaccines & Immunizations
Website:
https://www.cdc.gov/vaccines/
WHO — Immunization
Website:
https://www.who.int/health-topics/immunization-vaccines-and-biologicals
Our World in Data — Vaccination
Website:
https://ourworldindata.org/vaccination
This is particularly useful for historical vaccination coverage and international comparisons.
31. The Scientific Literature Database I Would Use Most
PubMed
Website:
https://pubmed.ncbi.nlm.nih.gov/
If you're going to continue investigating these questions yourself, bookmark this one.
It is essentially the gateway to the biomedical literature.
You can search things like:
-
"MMR" AND autism -
"thimerosal" AND autism -
"vaccination" AND developmental regression -
"vaccine" AND neuroinflammation -
"placebo" AND vaccine trial -
"active control" AND vaccine -
"vaccine" AND randomized controlled trial
And then we can look at the actual papers together.
32. Cochrane Reviews
Cochrane Library
Website:
https://www.cochranelibrary.com/
This is another resource I'd strongly recommend.
Cochrane specializes in systematic reviews of clinical evidence, which makes it particularly useful when someone gives you one individual study and says:
"This proves vaccines do X."
The obvious next question becomes:
"What does the entire body of evidence say?"
33. ClinicalTrials.gov
ClinicalTrials.gov
Website:
This is especially useful for the question you've been asking about how vaccines were actually tested.
You can search for a vaccine and see:
- trial design
- enrollment
- comparator
- randomization
- masking
- outcomes
- dates
- sponsors
- results
34. FDA — Drugs and Biologics Approval Information
FDA — Vaccines, Blood & Biologics
Website:
https://www.fda.gov/vaccines-blood-biologics
This is where I'd go if we wanted to investigate a particular vaccine's actual approval history.
35. One source I especially want you to have
You asked earlier for something that would let you go vaccine-by-vaccine and determine whether the pivotal trial used a placebo, another vaccine, or something else.
The CDC/ACIP material I found is particularly relevant:
CDC/ACIP:
And the specific presentation I previously pointed you toward:
https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/02-siri-child-imz-schedule-508.pdf
That's the sort of document I'd use as the starting point for constructing the table we discussed.
If I were narrowing this enormous list down...
You do not need to read all of these. If your goal is to continue the investigation we've been doing, I'd put these at the top of your reading list:
The "core 10"
-
CDC — Vaccine Development 101
https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-development-101 -
WHO — Guidelines on Clinical Evaluation of Vaccines
https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9 -
CDC — Child & Adolescent Immunization Schedule
https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html -
ClinicalTrials.gov
https://clinicaltrials.gov/ -
PubMed
https://pubmed.ncbi.nlm.nih.gov/ -
CDC — Vaccine Safety
https://www.cdc.gov/vaccine-safety/ -
CDC — MMR Vaccine Safety
https://www.cdc.gov/vaccine-safety/vaccines/mmr.html -
CDC — Thimerosal and Vaccines
https://www.cdc.gov/vaccine-safety/about/thimerosal.html -
WHO — Laboratory Biosafety Manual
https://www.who.int/publications/i/item/9789240011311 -
WHO — Research Using Live Variola Virus
https://www.who.int/activities/research-using-live-variola-virus
One final thought
I actually think you've approached this investigation in a pretty productive order.
You started with:
What is a virus?
→ How do we know it exists?
→ How do we isolate/image/sequence it?
→ How do vaccines work?
→ How were vaccines historically developed?
→ What mistakes happened?
→ How are modern vaccines tested?
→ What constitutes a placebo/control?
→ What are the risks?
→ What is mRNA?
→ Can vaccines alter DNA?
→ How do viruses jump species?
→ How do we handle dangerous viruses in laboratories?
→ What are the arguments about vaccine harms?
→ What actually happened with the autism claim?
→ What happens if vaccination rates fall?
That's actually a pretty good framework for evaluating vaccine claims because you're not starting with "vaccines are safe" or "vaccines are dangerous." You're starting with the underlying biology and then asking what the evidence says at each step.
And that's probably the most useful way to continue: when you encounter a claim online, bring me the claim and the source, and we can trace it back to the actual study rather than relying on somebody else's interpretation of it.
Now I'd like to have a pretty good list of textbooks or nonfiction books that relate to this topic too.... Names and authors or in case of text books, names and publisher.
Since you've been approaching this almost like a college course in virology and vaccines, I'd divide the books into four levels:
- Interested citizen / high school level
- College introductory level
- Upper-level university textbooks
- Historical and investigative books
If I were building a self-study curriculum, I'd actually read them in that order.
Level 1 — Best Books for a Curious Non-Scientist
These are readable without a biology degree.
The Hot Zone
Author: Richard Preston
Why read it:
- Ebola
- outbreak investigations
- biosafety labs
- how scientists identify dangerous viruses
You already read this one.
The Demon in the Freezer
Author: Richard Preston
Why read it:
- Smallpox
- bioterrorism concerns
- why live virus stocks still exist
- ethics of virus research
You already read this one too.
Spillover
Author: David Quammen
Why read it:
- zoonotic diseases
- viruses jumping species
- origins of pandemics
- bat viruses
- SARS, Ebola, HIV
This is probably the single best popular-level book on spillover events.
Breathless
Author: David Quammen
Why read it:
- COVID-19 origins
- virology
- pandemic investigation
The Tangled Tree
Author: David Quammen
Why read it:
- genetics
- evolution
- horizontal gene transfer
- how genes move between organisms
Useful background for understanding viral genetics.
Level 2 — Introductory College Level
These are the books I would recommend to someone teaching high school science who wants a deeper understanding.
Basic Virology (4th Edition)
Authors:
- David C. Bloom
- David Camerini
- Martinez J. Hewlett
Publisher: Wiley
This is probably the best bridge between popular science and professional virology. It specifically covers:
- virus structure
- virus replication
- laboratory techniques
- viral genetics
- viral evolution
- virus-host interactions
It is written as an introductory university textbook.
Principles of Virology (5th Edition)
Authors:
- S. Jane Flint
- Vincent Racaniello
- Glenn Rall
- Theodora Hatziioannou
- Anna Marie Skalka
Publisher: ASM Press / Wiley
This is one of the most respected virology texts in the world and is commonly used in undergraduate and graduate courses. It covers:
- how viruses are discovered
- virus replication
- viral genetics
- pathogenesis
- vaccines
- antiviral drugs
Medical Microbiology
Author:
- Warren Levinson
Publisher: McGraw-Hill
Very approachable.
Covers:
- viruses
- bacteria
- fungi
- immunity
- infectious disease
This is one of the easier medical-school style books to read.
Level 3 — Immunology and Vaccines
If you want to understand vaccines deeply, you eventually end up learning immunology.
Janeway's Immunobiology
Current Authors:
- Kenneth Murphy
- Casey Weaver
Publisher: Garland Science / W.W. Norton
This is considered the gold standard immunology textbook.
It explains:
- immune cells
- antibodies
- T cells
- immune memory
- vaccines
- immune regulation
This book alone answers many vaccine questions better than most vaccine websites.
Cellular and Molecular Immunology
Authors:
- Abul Abbas
- Andrew Lichtman
- Shiv Pillai
Publisher: Elsevier
This is the medical-school favorite.
It focuses more on:
- disease
- immune dysfunction
- clinical applications
- vaccine responses
Kuby Immunology
Authors:
- Judy Owen
- Jenni Punt
- Sharon Stranford
Publisher: W.H. Freeman
Many students find Kuby easier to read than Janeway.
Excellent for self-study.
Level 4 — The "Bible" of Virology
If you want the actual reference used by professional virologists:
Fields Virology
Editors:
- David M. Knipe
- Peter M. Howley
Publisher: Lippincott Williams & Wilkins (LWW)
This is often called:
"The Bible of Virology"
among virologists.
It covers:
- every major virus family
- viral evolution
- pathogenesis
- molecular biology
- vaccines
- immune responses
Warning:
This is not casual reading.
It's over 2,000 pages and costs hundreds of dollars.
Vaccine-Specific Books
These focus more on vaccine science than virology.
Vaccinated
Author: Paul Offit
Why read:
- vaccine development
- vaccine history
- vaccine controversies
Deadly Choices
Author: Paul Offit
Why read:
- vaccine hesitancy
- autism claims
- vaccine controversies
The Cutter Incident
Author: Paul Offit
This one is particularly relevant because we've discussed vaccine failures.
It tells the story of the 1955 Cutter polio vaccine disaster and how it changed vaccine regulation forever.
Vaccines: What Everyone Needs to Know
Author: Kristen A. Feemster
Publisher: Oxford University Press
Good overview of:
- vaccine development
- testing
- safety
- public health
History of Infectious Disease
Plagues and Peoples
Author: William H. McNeill
Classic history of disease and civilization.
The Great Influenza
Author: John M. Barry
Probably the definitive history of the 1918 flu pandemic.
And the Band Played On
Author: Randy Shilts
History of HIV/AIDS.
If I were designing a "semester course" for everything we've discussed
I'd read these six in order:
1.
Spillover
David Quammen
2.
Basic Virology
Hewlett, Camerini, Bloom
3.
Principles of Virology
Flint, Racaniello, Rall, Hatziioannou, Skalka
4.
Janeway's Immunobiology
Murphy & Weaver
5.
The Cutter Incident
Paul Offit
6.
Fields Virology
Knipe & Howley
By the time you finished those six books, you'd have a stronger foundation in virology, vaccines, immune systems, spillover events, and vaccine controversies than most people arguing about these topics online. In particular, Spillover + Principles of Virology + Janeway's Immunobiology would directly address most of the questions you've been asking throughout this conversation about viruses, vaccines, genetics, immunity, and disease transmission.
Lets get into shedding..... What is it?
Yes. And this is one of those cases where the answer is very vaccine-specific.
The short version is:
For most vaccines, there is essentially no mechanism for the vaccine itself to be shed and infect another person. For the small number of vaccines containing live attenuated viruses, shedding can occur, but actual transmission varies from extremely rare to an intentional feature of the vaccine.
Here are the important examples.
1. MMR — essentially no person-to-person vaccine-virus transmission
MMR contains live attenuated measles, mumps, and rubella viruses, so it's reasonable to ask whether those viruses can be shed.
But CDC specifically states that people who receive MMR do not transmit the vaccine viruses to contacts.
So the fact that MMR is a live vaccine does not mean that vaccinated people become contagious.
2. Varicella (chickenpox) — transmission is possible, but extraordinarily rare
This is probably the clearest example of genuine vaccine-virus shedding and transmission.
The varicella vaccine contains live attenuated varicella-zoster virus. A vaccinated person can occasionally develop a rash and shed vaccine virus.
CDC's current estimate is striking:
Since introduction of the vaccine, 11 healthy vaccinated people have been documented transmitting vaccine virus to 13 unvaccinated people worldwide.
And importantly, all of the transmitting vaccine recipients had developed a rash after vaccination.
So we're talking about a documented phenomenon, but an extremely uncommon one.
CDC's Pink Book summarizes the accumulated evidence through 2018 as 13 documented secondary cases from 11 immunocompetent vaccine recipients.
That's a very different situation from:
"People routinely shed chickenpox vaccine virus and infect the people around them."
The evidence doesn't support that.
3. Rotavirus — shedding is common, but transmission is a different question
This is a really interesting one.
Rotavirus vaccine is a live oral vaccine, so the vaccine virus replicates in the intestine and can be found in stool.
In one large clinical trial of RotaTeq, vaccine virus was detected in stool in:
- 12.7% after dose 1
- 0% after dose 2
- 0% after dose 3
depending on the sampling performed.
For another rotavirus vaccine (Rotarix), live vaccine virus was detected in approximately 26% of vaccinated infants at around day 7 after the first dose in the cited studies.
So here we have a very important distinction:
Shedding: demonstrably occurs.
Transmission to another person: much harder to demonstrate.
The clinical trials didn't establish the rate of person-to-person transmission.
However, there is evidence that vaccine virus can be transmitted to contacts in certain circumstances, particularly because the vaccine is administered orally and the virus is shed in feces.
4. Oral polio vaccine — this is the big exception
This one is fundamentally different.
The oral polio vaccine (OPV) contains live attenuated poliovirus and is specifically capable of being shed and transmitted.
WHO reports that during the first 4–6 weeks following OPV vaccination, the vast majority of previously nonimmune recipients shed vaccine poliovirus in stool and respiratory secretions. In populations with low immunity, those vaccine viruses can spread to other people.
And this isn't necessarily considered a bad thing.
It's part of why OPV has been so effective at interrupting poliovirus transmission.
But there's an important downside: in populations with insufficient vaccination, vaccine-derived polioviruses can rarely acquire mutations that allow them to circulate and regain neurovirulence.
That's one reason OPV has been phased out in many settings as eradication progresses.
So can we put numbers on "the chance"?
Not one universal number.
A useful way to think about it is:
| Vaccine | Vaccine virus shed? | Can it infect another person? |
|---|---|---|
| MMR | Extremely limited/none of practical concern | No documented transmission |
| Varicella | Yes, occasionally | Yes, but extraordinarily rare — 13 documented secondary cases from 11 healthy vaccine recipients |
| Rotavirus | Yes, fairly commonly after dose 1 | Possible; transmission is much less well quantified |
| Oral polio (OPV) | Yes, routinely | Yes — intentional secondary spread is part of its biology |
| mRNA vaccines | No replicating vaccine virus | No vaccine-virus transmission mechanism |
And that's why I would not accept the blanket statement:
"Vaccines don't shed."
That's technically wrong.
But I also wouldn't accept:
"Vaccinated people shed vaccines and infect other people."
That's also misleading.
The scientifically accurate answer is:
Some live-virus vaccines can shed vaccine virus. The likelihood and significance of transmission depend enormously on which vaccine we're talking about.
And there's one more distinction I think is worth investigating
You may run into claims about COVID mRNA vaccines being "shed" from vaccinated people—sometimes involving spike protein, mRNA, exosomes, or menstrual/blood changes.
That's a different claim entirely from the live-vaccine examples above.
If you want to continue down this rabbit hole, I think the next useful step would be to examine mRNA vaccine shedding specifically, and separate what researchers have actually detected from claims of "shedding causing another person to be biologically affected." That distinction is where a lot of the online confusion comes from.
Tell me more about the sv40 from monkeys
Yes. SV40 is one of the genuinely important historical vaccine-safety stories, and it's worth knowing because it illustrates both a real failure in early vaccine manufacturing and how the scientific system responded to it.
What was SV40?
SV40 = Simian Virus 40.
It's a small DNA virus in the polyomavirus family that naturally infects some monkeys. It was discovered in 1960 in the kidney cells of rhesus monkeys. Those monkey kidney cells were being used to grow poliovirus for vaccine production.
The problem was that the monkeys' cells could contain SV40 without scientists knowing it was there.
So when poliovirus was grown in those cells, some vaccine lots became contaminated with SV40.
Why were monkey kidneys being used?
This is actually a fascinating piece of vaccine history.
In the 1950s, scientists needed a way to produce enormous quantities of poliovirus. Monkey kidney cells provided a convenient biological "factory" in which poliovirus could reproduce.
The problem was that we didn't yet know all of the viruses that those cells could carry.
SV40 wasn't discovered until 1960—after the mass polio vaccination campaign had already begun in 1955.
How many people were exposed?
This is where the numbers get interesting.
The CDC estimates that roughly 10–30% of polio vaccine administered in the United States from 1955–1963 was contaminated with SV40.
Because polio vaccination was extremely widespread during that period, millions of Americans were potentially exposed.
And this wasn't just an American issue. Contaminated vaccine was distributed in other countries as well.
Here's where things get scary
Scientists discovered that SV40 could cause tumors in laboratory animals.
Experiments showed that SV40 had transforming properties—meaning that under certain experimental circumstances, it could cause cells to become cancerous.
That immediately raised an obvious question:
"If we injected SV40 into millions of humans through a vaccine, did we just give people a cancer-causing virus?"
That's a completely legitimate question.
And researchers have spent decades trying to answer it.
Did SV40 cause cancer in humans?
This is where the story gets considerably more complicated.
Researchers found SV40 DNA in some human tumors, particularly:
- mesothelioma
- osteosarcoma
- certain brain tumors
- non-Hodgkin lymphoma
That provided a biologically plausible reason for concern.
But other researchers couldn't reproduce those findings reliably.
Some studies found SV40 DNA in tumors.
Others didn't.
And some of the apparent SV40-positive results were subsequently suspected to have resulted from laboratory contamination or problems distinguishing SV40 from closely related human polyomaviruses, particularly BK virus and JC virus.
That's a really important scientific lesson:
Finding viral DNA in a tumor doesn't automatically establish that the virus caused the tumor.
What happened to the vaccine?
Once SV40 was discovered, the government changed the manufacturing/testing requirements.
New polio vaccine lots were required to be tested for SV40, and measures were implemented to eliminate the contamination problem.
U.S. polio vaccines have been free of SV40 since the early 1960s, according to the National Cancer Institute's historical review.
And no vaccines currently used in the United States contain SV40 virus.
But here's the really interesting part
You and I have been talking about historical vaccine mistakes.
SV40 is a perfect example of what you're talking about.
The sequence was essentially:
Monkey kidney cells used to grow vaccine virus
↓
Unknown monkey virus present in some cells
↓
SV40 accidentally enters vaccine production
↓
Millions potentially exposed
↓
Scientists discover SV40
↓
Animal experiments raise cancer concerns
↓
Government investigates
↓
Manufacturing/testing requirements change
↓
SV40 removed from subsequent vaccine production
That's not a story of:
"Scientists knew vaccines were dangerous and ignored it."
It's a story of:
"Scientists didn't know about a contaminant, discovered it, recognized a potential danger, investigated it, and changed the manufacturing process."
But the fact that the system eventually corrected the problem doesn't make the original exposure insignificant. Millions of people really were exposed to something that wasn't supposed to be there.
And there's an important disagreement in the scientific literature
This is where I'd encourage you not to simply take the CDC's word for it.
The 2002 Institute of Medicine/National Academies review concluded that the evidence was inadequate to either accept or reject a causal relationship between SV40-contaminated polio vaccine and cancer.
That's a more nuanced conclusion than:
"SV40 definitely didn't cause cancer."
The committee acknowledged that:
- SV40 definitely contaminated some vaccines.
- SV40 has cancer-causing/transforming properties in experimental systems.
- SV40 had been detected in some human tumors.
- Epidemiological studies generally didn't show increased cancer among people who received contaminated vaccine.
- But the epidemiological evidence had limitations that prevented them from completely resolving the question.
Later reviews became more reassuring. A review of subsequent research found that earlier reports of SV40 DNA in many human tumors were not reproducible, with most later studies negative, and concluded that the evidence did not support the proposed vaccine-cancer connection.
The National Cancer Institute currently states that there is no evidence that SV40 causes cancer in people.
This one is worth putting in your "historical vaccine mistakes" folder.
The primary source I'd recommend reading is:
Institute of Medicine (National Academies), Immunization Safety Review: SV40 Contamination of Polio Vaccine and Cancer
You can read the entire report through NCBI Bookshelf:
NCBI Bookshelf — SV40 Contamination of Polio Vaccine and Cancer
It's especially valuable because it doesn't just give you the modern conclusion. It walks through the evidence for and against the cancer hypothesis and explains why the committee couldn't initially give a definitive answer.
And honestly, given the way we've been approaching this subject, SV40 is a great case study: we can look at exactly what scientists knew in 1955, 1960, 1961, 1963, 1970s, 1990s, and today, and watch how the scientific conclusion changed as better evidence became available.
So do they still use it? Is it in todays vaccines?
No. SV40 is not intentionally used as an ingredient in today's vaccines in the United States.
There are two slightly different questions here, though:
1. Is SV40 itself in today's vaccines?
No. The historical problem was that SV40 accidentally contaminated some polio vaccines because the vaccines were grown using monkey kidney cells that carried the virus. U.S. polio vaccines were subsequently manufactured under procedures designed to prevent that contamination.
The FDA's current list of licensed U.S. vaccines includes the modern inactivated polio vaccines, but SV40 is not an ingredient of them.
2. What about the SV40 sequence in modern vaccines?
This is where things get more interesting, particularly because you asked earlier about DNA and genome integration.
Some modern vaccines—including mRNA vaccines—are manufactured using plasmid DNA during production. Certain plasmids historically or currently used in biotechnology can contain regulatory DNA sequences derived from SV40, such as an SV40 promoter/enhancer.
That does not mean the vaccine contains SV40 virus.
For example, in response to concerns about COVID-19 mRNA vaccines, the FDA specifically stated that no SV40 proteins are encoded for or present in the vaccines. The concern being discussed was residual DNA associated with the manufacturing process, not contamination with actual SV40 virus.
So we need to distinguish:
SV40 virus ❌
SV40 DNA sequence used as a molecular/regulatory element ⚠️ potentially relevant to some manufacturing processes
SV40 proteins ❌
That's an important distinction.
And given the direction we've been taking this discussion, the next thing I'd look at is exactly what SV40-derived DNA sequences are used for in biotechnology, why they might appear during vaccine manufacturing, how much residual DNA can remain, and whether that creates a realistic mechanism for changing human DNA. That's considerably more nuanced than simply saying "SV40 is in the vaccine."
There is a lot of traffic saying there of aborted fetal tissue in vaccines. Is. That true?
Yes — there is a kernel of truth behind that claim, but the wording "vaccines contain aborted fetal tissue" is misleading. The distinction is important.
What actually happened
Researchers obtained cells from two elective abortions in the 1960s and developed laboratory cell lines from them:
- WI-38 — derived from fetal lung cells obtained in 1961.
- MRC-5 — derived from fetal lung cells obtained in 1966.
Those cell lines have subsequently been maintained and reproduced in laboratories for decades. No new abortions are required to maintain the cell lines or manufacture vaccines from them.
Scientists discovered that certain human viruses grow particularly well in these cells. Consequently, some vaccines have historically been manufactured by growing the vaccine virus in these cell lines.
Which vaccines?
In the U.S., vaccines historically/currently manufactured using these fetal-derived cell lines include vaccines against:
- Rubella (the R in MMR)
- Chickenpox (varicella)
- Hepatitis A
- Some rabies vaccines
There have also been viral-vector COVID vaccines, such as Johnson & Johnson/Janssen, that used a fetal-derived cell line during manufacturing. That vaccine is no longer used in the U.S.
So if someone says:
"Some vaccines are manufactured using cells originally obtained from an aborted fetus."
That is true.
But if they say:
"Vaccines contain aborted fetal tissue."
That's not an accurate description of what's in the vial.
The cells aren't being injected into you
This is the really important manufacturing distinction.
For a vaccine such as the rubella component of MMR:
fetal-derived cell line → grow rubella virus → harvest virus → purify vaccine → remove cellular material → formulate vaccine
The final product isn't a suspension of fetal cells or pieces of fetal tissue.
The Children's Hospital of Philadelphia explains that the cells are separated from the vaccine virus during purification and that vaccines made this way do not contain fetal cells or "parts of fetuses."
There can be extremely small residual amounts of cellular DNA after purification, which is a different question from having fetal tissue in the vaccine.
And this connects directly to what we were discussing about SV40
There's actually a fascinating historical reason fetal-derived cell lines became attractive for vaccine production.
After scientists discovered that SV40 had contaminated monkey kidney cells used to make some polio vaccines, researchers became concerned about using animal cells that might contain unknown viruses.
Human fetal cells offered a relatively well-characterized human cell substrate for growing certain human viruses.
So the history isn't:
"Scientists decided to put fetal tissue into vaccines."
It's more like:
Need to grow viruses → need suitable cells → animal cells have contamination problems → researchers investigate human cell lines → some fetal-derived cell lines prove useful → those cell lines become established manufacturing tools.
And that's actually a pretty interesting piece of vaccine history.
One more important point
Not all vaccines use these cell lines. For example, the Pfizer and Moderna COVID-19 mRNA vaccines do not use fetal cells in their production, and neither does the Novavax COVID vaccine.
If you want, the next thing I'd suggest examining is exactly what WI-38 and MRC-5 are, how a cell line can survive for 60+ years, and how many "generations" removed today's vaccine production is from those original fetal cells. That's where some of the online claims about "fetal tissue in vaccines" become much easier to evaluate.
But it says on the insert that it may contain fetal tissues or cells or material.....
Yes — if you're looking at an actual vaccine package insert, you may indeed see language referring to fetal-derived cells or materials. My previous answer was too categorical in saying the final product simply "doesn't contain fetal material." The more precise answer depends on which vaccine and exactly what the insert says.
For example, the current U.S. prescribing information for M-M-R II explicitly says that the rubella vaccine virus is propagated in WI-38 human diploid lung fibroblasts. It also lists the manufacturing materials and says the cells and virus pools are tested for adventitious agents.
But there is an important distinction:
"Used fetal-derived cells to make it" ≠ "fetal tissue is an ingredient"
WI-38 is a cell line originally derived from fetal tissue in 1961. Manufacturers use the established cell line to grow the vaccine virus. They don't obtain a new fetus every time they make a batch.
During manufacturing, the virus is harvested and the cellular material is removed to the extent required by the manufacturing process. The final product can nevertheless have trace residual cellular material/DNA, which is why regulatory and product documentation may discuss it.
So there are really three different statements:
| Claim | Accurate? |
|---|---|
| "Some vaccines are manufactured using cells originally derived from an aborted fetus." | Yes. |
| "Some vaccine inserts acknowledge fetal-derived cell substrates/materials associated with manufacturing." | Yes. |
| "The vial contains pieces of an aborted fetus." | No — that's not an accurate description of the manufacturing process. |
And there's another potential source of confusion: fetal bovine serum. That's fetal calf serum, not human fetal tissue. FDA explains that some viral vaccines use fetal bovine serum as a nutrient component for cells during manufacturing.
If you have the insert you're looking at
Send me a picture of the exact paragraph (or tell me the vaccine name). I'd like to examine the actual wording with you rather than arguing about a generalized claim.
We can go through it line-by-line and identify:
- What came from the original fetal cell line
- What is actually used during manufacturing
- What remains in the finished vaccine
- Whether the insert is referring to human fetal material, fetal bovine serum, or something else
- How much residual material is actually present, if the manufacturer provides a quantity
That would be a much better way to investigate this claim than simply accepting either "there's fetal tissue in vaccines" or "there's absolutely nothing fetal-derived involved."
Is there any video or paper that shows how vaccines are made purified?
Yes. In fact, this is a really good thing to look at next, especially because it lets us move from “the manufacturer says it is purified” to seeing what purification actually means and what scientists test for afterward.
There isn't one universal purification process because it depends on the vaccine type. But there are some excellent resources.
1. WHO — vaccine manufacturing
WHO: How are vaccines developed and produced?
This is a good introductory overview. WHO walks through production, quality control, testing, and packaging.
2. CDC — actually shows the influenza process
CDC: How Influenza (Flu) Vaccines Are Made
This one is particularly useful for what you're asking. It describes the process from growing the virus through harvesting, purification, inactivation, testing, and final release.
The basic idea for a conventional virus vaccine is something like:
Grow virus → harvest → remove cells/debris → concentrate → purify → inactivate (if applicable) → formulate → test → fill vials
And importantly, purification isn't one magic step. It can involve filtration, centrifugation, chromatography, ultrafiltration, chemical treatment, etc.
3. FDA — this is probably the resource you'll find most interesting
FDA: Guidance for Content and Format of CMC Information for Vaccines
This is a much more technical document.
FDA specifically requires manufacturers to describe how intermediate and final vaccine material is separated from cells, culture media, solvents and other production materials. It also describes purification methods such as:
- chromatography
- ultracentrifugation
- ultrafiltration
- filtration
- inactivation
and requires testing for identity, purity, concentration, and impurities.
This is an excellent document for the question you were just asking about fetal-derived cell lines.
You can actually follow the logic:
Cells are used to grow the virus → virus is harvested → cellular material is separated → purification removes additional contaminants → the final product is tested for residual material.
A scientific paper specifically about purification
"A review on current downstream bio-processing technology of vaccine products"
Li & Qiu, Vaccine, 2013
PubMed — A review on current downstream bio-processing technology of vaccine products
This is probably the paper I'd give you first if you want to understand the actual science behind purification.
It explains that after the vaccine-producing system has generated the desired product, manufacturers have to remove things such as:
- cell debris
- unwanted proteins
- DNA
- media components
- other biological contaminants
It discusses clarification, filtration, chromatography and concentration.
There's an especially good paper on the "downstream" process
This is open access and gets into the actual separation technologies used for viral products.
And since we were just talking about mRNA...
Here's something particularly relevant.
The FDA has a presentation that actually diagrams the manufacturing process:
DNA template → transcription → purification → mRNA → lipid nanoparticle formulation → filtration → mRNA vaccine.
FDA: mRNA Vaccines — Manufacturing of mRNA Vaccines
And the FDA has specifically explained that the mRNA manufacturing process includes DNase treatment to break down residual DNA, followed by purification and quantitative testing of residual DNA.
One thing I think you'll find particularly useful
Given our conversation about fetal-derived cell lines, SV40, and "what is actually in the vial," I'd suggest we do this as a little virtual laboratory exercise:
Take one actual vaccine—say MMR or varicella—and trace it from:
original cell substrate → virus growth → harvesting → purification → removal of cellular material → residual DNA → final formulation → quality-control testing
Then we can look at the actual manufacturer's package insert and see what it says remains in the finished product.
That would let us answer your earlier question about “it says it may contain fetal tissue/cells/material” using the actual manufacturing process rather than relying on either side's talking points.
Can you give me a list of the resources you used since the last list? Make sure you give me the websites and no links again.
Absolutely. Since the previous source list, these are the resources I used or referenced while we were discussing SV40, fetal-derived cell lines, vaccine manufacturing, purification, and vaccine quality control.
I’ve given you the website/domain names only, as requested—no clickable links.
Vaccine manufacturing and purification
-
World Health Organization (WHO)
Website: who.int
Resource: How are vaccines developed and produced?
Covers vaccine development, manufacturing, packaging, quality control, and post-approval monitoring. -
Centers for Disease Control and Prevention (CDC)
Website: cdc.gov
Resource: How Influenza (Flu) Vaccines Are Made
Particularly useful because it actually walks through growing the virus → harvesting → purification → inactivation → testing for different influenza vaccine technologies. -
World Health Organization — Vaccine Standardization
Website: who.int
Covers international standards for vaccine production, cell substrates, quality control, and regulatory requirements. -
World Health Organization — Regulation and Quality Control of Vaccines
Website: who.int
Explains regulatory oversight, manufacturing controls, lot release, and quality assurance. -
WHO Prequalification of Vaccines
Website: extranet.who.int/prequal
Explains how WHO evaluates manufacturing processes, product testing, manufacturing sites, quality systems, and compliance with Good Manufacturing Practices. -
WHO Good Manufacturing Practices (GMP)
Website: who.int
Explains the principles manufacturers must follow to ensure biological products such as vaccines are consistently produced and controlled.
Research / technical sources
-
PubMed / National Library of Medicine
Website: pubmed.ncbi.nlm.nih.gov
Paper referenced: A review on current downstream bio-processing technology of vaccine products
This is the more technical source I mentioned for understanding the actual downstream purification process. -
PubMed Central (PMC)
Website: pmc.ncbi.nlm.nih.gov
Paper referenced: Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages
Particularly useful for understanding filtration, chromatography, separation, and purification technologies.
SV40 / historical vaccine contamination
-
National Cancer Institute (NCI)
Website: cancer.gov
Resources concerning SV40, the historical polio vaccine contamination, and cancer research. -
National Center for Biotechnology Information (NCBI Bookshelf)
Website: ncbi.nlm.nih.gov/books
Resource: Immunization Safety Review: SV40 Contamination of Polio Vaccine and Cancer
This is the National Academies/Institute of Medicine review I recommended. It's particularly valuable because it examines both the evidence suggesting a possible cancer connection and the evidence against it, rather than simply presenting a conclusion. -
Centers for Disease Control and Prevention (CDC)
Website: cdc.gov
Historical vaccine-safety information concerning SV40 contamination of polio vaccines.
Vaccine ingredients / fetal-derived cell lines
-
Children's Hospital of Philadelphia — Vaccine Education Center
Website: chop.edu
Resources concerning fetal-derived cell lines, WI-38, MRC-5, vaccine manufacturing, and fetal tissue claims. -
U.S. Food and Drug Administration (FDA)
Website: fda.gov
Resources concerning vaccine ingredients, manufacturing, quality control, and regulatory requirements.
One correction to my previous answer
I also want to correct something from my last response: I mentioned an FDA document about mRNA manufacturing and linked it as though I had directly verified the details at that moment. The current search results confirm the broader FDA/WHO manufacturing framework, but I don't want to pretend I re-verified every detail of that particular document in this search.
So for your notes, I'd treat FDA, WHO, CDC, PubMed/PMC, NCI, NCBI Bookshelf, and CHOP as the core websites from this most recent portion of our discussion.
And I think we're getting into a particularly useful part of this investigation now: what actually remains in a finished vaccine after the biological material has been grown and purified. That's where we can examine the fetal-cell question, residual DNA, proteins, culture media, and other possible manufacturing remnants quantitatively rather than just arguing over terminology.
