The Nature Article “The tangled history of mRNA vaccines” CORRECTION
I wrote this letter to Nature. (email@example.com) about the article titled “The tangled history of mRNA vaccines” and am sharing my letter here. If anyone else wanted to write to Nature about this issue I would be very appreciative of the support.
BTW: I am sorry for the length of this post- but the need to document the early history is important.
The Correction follows:
Dear Editor (of Nature),
First, I wish to thank you for publishing the article in Nature titled “The tangled history of mRNA vaccines”, in September, 2021
By way of introduction, I am the wife of 42 years of Robert Malone, MD, who is prominently featured in the article and I was witness to all the early events (as scientist and wife).
It is very important to have an accurate timeline of events. For the original mRNA transfection experiments, the article was good and I sincerely thank Nature for that. However, the article has just tangled the history even further and needs to be corrected.
Unfortunately, the article’s timeline is not correct. The timeline and inventorship of the first animal experiments is very wrong. Egregiously wrong. The first proof of principle experiment of mRNA vaccination in an animal model was clearly conducted in 1989 and 1990 by the inventors on the original patents, which included Robert Malone. The proof of principle experiment in animals can be found in the original patents. Patents have always been a way to prove inventorship. An approved patent must have clear scientific data to support the claims. A claim for a patent is NEVER approved on an idea, it MUST be reduced to practice. This is the backbone of US patent law. In this case, the claims approved are clearly indicated for mRNA vaccination.
The Nature article states that the first animal experiment was done in 1992 by another group. THIS IS FALSE.
For some background. The way that a patent is approved, experimental data must be sent to the USPTO within a year of the filing of the patent application. The patent examiner analyzes the evidence and approves or disproves a claim based on the data presented and the USPTO does a literature and patent search to ensure this is a novel invention. This is how the USPTO operates then and now.
In order for the patent to be approved, Vical provided the proof of principle experimental study results for mRNA vaccination in animals. That happened within a year of March 21, 1989. If they had not sent in the data within a year, the patent examiner would have not approved the claim of the invention of mRNA vaccination. Patents are NOT approved on ideas. alone Proof must be provided, that is examined for prior “art.” Only then can a patent claim be approved.
In the case of mRNA vaccines, this proof of principle experiment was first conceived by Robert and then designed by Robert and Dr. Gary Rhodes. Robert provided some of the materials needed from his bench, Gary provided some and the animal experiments were conducted by Gary. Robert trained and helped Gary design the original mRNA and DNA vaccine experiments. The research resulted in the experiment titled: “mRNA Vaccination of Human Stem Cell-bearing SCID Mice with NEF mRNA followed by HIV Challenge” that is found in the original patents. This is unequivocally the first animal experiment using mRNA vaccination, and included an animal challenge model. It happened early 1989 and 1990, NOT 1992 as your inaccurate article states.
Here is the FIRST ANIMAL VACCINE EXPERIMENT, CONDUCTED IN 1989/1990:
Experimental data found in
US PATENT #US5580859A, US5589466A, US6214804B1and about 6 other patents, all with a priority date of 1989.
Induction of a protective immune response in a mammal by injecting a DNA sequence
A method for delivering an isolated polynucleotide such as DNA or RNA, to the interior of a cell in a mammal comprising the injection of an isolated polynucleotide into a muscle of the mammal where the polynucleotide is taken up by the cells of the muscle and exerts a therapeutic effect on the mammal. The method can be used to deliver a therapeutic polypeptide to the cells of the mammal, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the mammal or to provide transitory gene therapy.
mRNA Vaccination of Human Stem Cell-bearing SCID Mice with NEF mRNA Followed by HIV Challenge
Severe combined immunodeficient mice (SCID mice (Molecular Biology Institute, (MBI), La Jolla, Calif. 92037)) were reconstituted with adult human peripheral blood lymphocytes by injection into the peritoneal cavity according to the method of Mosier (Mosier et al., Nature 335:256 (1988)). Intraperitoneal injection of 400 to 4000 infectious units of HIV-1 was then performed. The mice were maintained in a P3 level animal containment facility in sealed glove boxes.
mRNA coding for the nef protein if HIV was prepared by obtaining the nef gens in the form of a plasmid (pGM92, from the NIAID, Rockville, Md. 20852); removing the nef gene from the plasmid; inserting the nef gene in the pXBG plasmid for transcription; and purifying the transcription product nef mRNA as described in Examples 2 through 5. The nef mRNA was then incorporated into a formulation according to Example 6. 200 microliter tail vein injections of a 10% sucrose solution containing 200 ug/ml NEFRNA and 500 ug/ml 1:1 DOTAP:DOPE (in RNA/liposome complex form) were performed daily on experimental animals, while control animals were likewise injected with RNA/liposome complexes containing 200 ug/ml yeast tRNA and 500 ug/ml 1:1 DOTAP/DOPE liposomes. At 2, 4 and 8 weeks post injection, biopsy specimens were obtained from injected lymphoid organs and prepared for immunohistochemistry. At the same time points, blood samples were obtained and assayed for p24 levels by means of an ELISA kit (Abbott Labs, Chicago, Ill.) and virus titer by the plaque assay of Example 8. Immunostaining for HIV-1 was performed as described (Namikawa et al., Science 242:1684 (1988)) using polyclonal serum from a HIV infected patient. Positive cells were counted and the number of infected cells per high power field (400x) were determined. Using these assays, at least a 2 fold reduction in the number of positive staining cells was observed at 8 weeks, and titer and p24 expression was reduced by at least 50%. Together, these results indicate a moderate anti-viral effect of the (in vivo) treatment. A volume of 200 μl of the formulation, containing 200 μg/ml of nef mRNA, and 500 μg/ml 1:1 DOTAP:DOPE in 10% sucrose is injected into the tail vein of the human stem cell-containing SCID mice 3 times in one day. Following immunization, the mice are challenged by infection with an effective dose of HIV virus. Samples of blood are periodically withdrawn from the tail vein and monitored for production of the characteristic HIV protein p24 by an ELISA kit assay (Abbott Labs, Chicago, Ill.).
BTW – the original data from example 9 was sent from Vical to the USPTO on March 21, 1990 and I have the original data packet (which can be found on my website).
This patent application (along with the others) was sent to the USPTO on March 21, 1989. From there, they had a year to provide study results to the USPTO. The results of that experiment were sent to be USPTO on 21 March, 1990. The US Patent Office approved those claims with a priority date of March 21, 1989, meaning the experiment had to be conducted prior to March 21, 1990. This is clear proof that that the first mRNA vaccination in rodents happened before March 21, 1990.
If the published experiment that you list as the first, was the first in animals, those claims would have been disproved by the USPTO. That is how it works. What you have written is not only misleading, it is wrong and needs to be corrected immediately.
This is the backbone of one of Robert’s biggest complaints is no one will recognize that the USPTO approved the claim of mRNA vaccination based on the study results that were clearly the first proof of principle animal experiment. Why wasn’t this mentioned in the article? Was it purposeful? Did you not know how the patenting process works?
As Vical never allowed the researchers (including Robert) to publish these results in a peer reviewed paper, the patents are the first proof of principle of the mRNA experiments in an animal model. Patents are considered to be arbiters of proof of inventorship. I believe that Nature is well aware of this. These patents have been cited 1000s of times (particularly for DNA vaccines in the 1990s) in scientific literature. They were not hard to find or review.
One of Robert’s complaints has always been that this critical proof of principle experiment is not cited as the first in animal experiment of mRNA vaccination. How did this get missed (AGAIN)!!! Was it purposeful? It sure feels that way!
This claim and the study results provide concrete proof that this was the FIRST mRNA vaccine experiment in animals and it was conducted in mice in 1989/1990!!!
Again, I am not sure how and why this is missed?
The experimental results are right there in the patents. It is clear, concrete proof of principle and data had to be supplied to the USPTO within a year of the patent filing.
Note – that this erroneous timeline was first published in a review article by Weisman in 2018
Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov. 2018 Apr;17(4):261-279. doi: 10.1038/nrd.2017.243. Epub 2018 Jan 12. PMID: 29326426; PMCID: PMC5906799.
Since then, this false narrative and timeline has been propagated throughout the web and other science papers, including WIKI. As Dr. Weisman is not an unbiased person in this history (I will not discuss his motivations in this, but they should be clear), this should never have been allowed to be published. Someone has to have the backbone and be willing to get it right. I hope it will be Nature.
an you explain to me why this was not listed as the first experiment of mRNA vaccines in an animal model?
How can this gross oversight be allowed to continue in the scientific press?
What will Nature do to correct this article?
Dr. Jill Glasspool Malone
I have clipped out the animal experiment from one the patents as a screenshot, but I encourage you to go to any of the patents and review for yourself.
Also, here is the website that lists most of the patents and links to them.
Here is a link to the first patent issued (note the priority date of March 21, 1989) and go to example 9.
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