So, it finally happened. And with the announcement came yet another wave of troll and bot attacks on my credibility. Coupled with social media calls for me to comment on the event. Commenting on which I am generally not comfortable with, because I am not prone to pettiness. Jill and I gave ourselves a day to just breathe, discuss the meaning and implications, and process and respond to the many kind, supportive comments and condolences from friends and colleagues from all over the world.
First off, congratulations to Drs. Kariko and Weissman. This award comes on top of having received the Lasker award, and similar awards from the governments of Spain and Israel.
A day in, I think that the proper way to approach commenting on this is to examine the truthfulness of the official statements made by the Nobel Committee concerning their decision.
First off, the core position that has been taken is to not assert that Kariko and Weissman were the originators or inventors of the use of mRNA to elicit an immune response (vaccination). I suppose that there is a small modicum of validation in that. As I have often had to explain in so, so many podcasts and press interviews, inventorship of the manufacturing, structure and use of mRNA for vaccine purposes was long ago determined by the US Patent and Trademark office, with many US and foreign patents issued based on the work of myself (1987- 1991) and colleagues (1990-1991), all of which (including the initial invention disclosures which I solo authored) list me as an inventor. That fact is not disputed by the Nobel committee. It is extremely unusual for the Nobel Prize in Physiology or Medicine to not recognize those that originated the ideas, technology, and performed initial proof of concept. This appears to have been circumvented in this case by limiting the scope of the award to the COVID-19 mRNA vaccines themselves, and not to the discoveries and inventorship of the platform technology.
The key statement by the committee is quoted in their announcement tweet and corresponding graphic:
“For their discoveries concerning nucleotide base modifications that enabled the development of effective mRNA vaccines against COVID-19”
There are three logic elements to the statement.
- “Discoveries concerning nucleotide base” refers to the incorporation of pseudouridine in place of uridine throughout an in vitro transcribed (synthetically produced) mRNA. Which results in a molecule which is quite different in many key biological properties from natural mRNA, but can still be translated into protein. The work in question is described in three publications and a patent. In contrast to my original work and patents none of which discuss use of this for vaccine development, which occurred 15 years prior to the initial publication.Karikó, K., Buckstein, M., Ni, H. and Weissman, D. Suppression of RNA Recognition by Toll-like Receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).
Karikó, K., Muramatsu, H., Welsh, F.A., Ludwig, J., Kato, H., Akira, S. and Weissman, D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther 16, 1833–1840 (2008).
Anderson, B.R., Muramatsu, H., Nallagatla, S.R., Bevilacqua, P.C., Sansing, L.H., Weissman, D. and Karikó, K. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38, 5884–5892 (2010).
- “Enabled the development” is actually a false statement. The incorporation of pseudouridine was not an “enabling” improvement on the existing state of the art. This is demonstrated by the robust clinical (human) adaptive antibody vaccine response to the CureVac SARS-CoV-2 vaccine candidate, which did not incorporate pseudouridine. The dose (and apparently the toxicity) of the mRNA formulation employed by CureVac in their clinical tests was lower than that employed by Moderna and BioNTech, and the antibody titers were also lower. But still quite substantial. There is no evidence that antibody titer translates to clinical protection from SARS-CoV-2 infection or COVID-19 disease, but despite this fact it was widely inferred and publicized that the CureVac product was inferior. Whether or not this was the case we will never know, as further clinical testing at a higher dose was not performed- CureVac basically gave up on competing in the COVID-19 vaccine race, presumably due to lack of sufficient funds. However, there is no disputing the fact that incorporation of pseudouridine is not required for delivered mRNA to elicit an adaptive immune (antibody) response. In sum, the claim that pseudouridine incorporation is an “enabling” improvement on prior art (that being patent and inventorship language) is clearly false for this reason.
- “Effective mRNA vaccines against COVID-19” is a very controversial statement. The basis cited by the committee for this assertion is included in the corresponding press release (attached below). “Protective effects of around 95% were reported” refers to the initial interpretation of the clinical trial results obtained, both the interpretation of which and the trials themselves have since been shown to have been fraudulent. This statement is not consistent with current understanding of those trial results, but rather reflects initial propaganda subsequently demonstrated to be highly misleading. “The vaccines have saved millions of lives and prevented severe disease in many more” is also not fact based, but rather is also often repeated propaganda. This assertion is largely based on the difference between initial analysis and modeling data suggesting a 3.4% case fatality rate for SARS-CoV-2 infection, subsequently shown to have been highly inflated, and the current best estimates of case fatality rates which are in the range of a fraction of 1%. This difference has been asserted to be the consequence of vaccine efficacy, but this is not supported by actual clinical epidemiology data. Current analyses based on all cause mortality data actually indicate either no effectiveness of the vaccines or negative effectiveness (multiple studies demonstrate that the onset of vaccination campaigns (both general types and mRNA genetic types) are correlated with an increase in all cause mortality, not a decrease). In addition, data from many different databases indicate negative effectiveness for these mRNA-based products beginning from two to seven months after administration. Negative effectiveness in this case refers to the observation that recipients are more likely to be hospitalized with COVID-19 than those not receiving these mRNA – based products.
- To the extent that there was a relevant enabling improvement on the work of myself and my named co-inventors from the 1987-1991 time frame, that would be the formulation advancements of Dr. Pieter Cullis and colleagues at the University of British Columbia. Not the incorporation of pseudouridine. Dr. Cullis and colleagues were not included in this award decision.
- The remarkably rapid development and deployment of these mRNA products parallel and correspond to the timelines achieved by other more traditional COVID-19 vaccines (“Sputnik” series etc.). This is not the consequence of the mRNA/pseudouridine technology, but rather to the willingness of regulatory authorities worldwide to suspend normal vaccine non-clinical and clinical development processes required to assess safety and efficacy. The committee asserts that these vaccines were “approved” as early as December 2020, which is another falsehood. These products were Emergency Use Authorized via suspension of normal testing, processes and review.
- The demonstrable falsehoods employed by the Nobel Prize committee to justify this award indicates that the decision was not based on scientific and medical fact, but rather reflects non-scientific and medical considerations other than those cited by the committee.
- Pfizer is a major donor to the Karolinska Institute.