Mind the Gap in Science and Therapeutics

Dear Professor Siddhartha Mukherjee,

            I fully enjoyed reading your book The Emperor of All Maladies ten years ago when I was in South Africa, and recently bought your new book The Song of the Cell. I am an autodidactic AIDS, Ebola, and Covid researcher who has been HIV+ since 1983 and participated in the MACS AIDS study at UCLA from 1984 until 2015. In 2014 I provided the Liberian Ministry of Health the only medicine that showed a significant benefit against Ebola during the entire 2014-2016 West African Ebola epidemic. Added to the WHO standard of care for Ebola, 1.2mg of selenium reduced the mortality rate by 42.8% compared to the WHO standard alone.

            When I noticed The Song of the Cell at the bookstore, I examined the index to see if it included the subjects I focus on. I looked for NF-kB, selenium, and antioxidants. None of those were mentioned. I bought it anyway. As expected, your book did not disappoint. It is excellent. However when I finished “The Pandemic” chapter, I felt the overwhelming urge to write to you to help fill a gap in the knowledge base.

            One aspect of your book’s narrative I enjoyed was your recitation that time after time, historically important discoveries were immediately rejected by the medical establishment. Novel insights frequently originate from the periphery of medicine or lower in the ranks of the medical hierarchy. How could a mere draper invent the microscope? However, like me, Leeuwenhoek was a letter writer. Having read numerous histories of medicine, discovery by those who are outside the professional elite is a constant theme. That theme gives me the determination to continue writing. My next book will be titled, Redefining AIDS including the chapter “How HIV Causes AIDS”. That has been another gap in our knowledge. On that I agree with Dr David Ho who highlighted that unrecognized gap in knowledge in his keynote address to the First International Scientific Conference on AIDS in June 2001 in Buenos Aires, Argentina.     

            Living in Los Angeles in September 1981 I read the first article ever published in the LA Times about the new mysterious disease that was attacking gay men. That was the second article ever published in the US about HIV, following the first in the New York Times. In 1980 a coworker at the Defense Logistics Agency Los Angeles was already coming down with AIDS and KS. In mid-January 2020, in Johannesburg SA, the instant I heard a new flu-like disease of unknown origin causing pneumonia had erupted in Wuhan I knew it was happening again. By the end of January I had written my first commentary about this emerging pandemic and emailed it to English speaking newspapers across Southern Africa. I continued monitoring the progress of the pandemic and writing newspaper commentaries until I returned to the United States in April 2022.

            As an autodidactic scientific analyst I humbly acknowledge my limits, but I do know the science.  I have read over three thousand medical journal articles on viral disease and immunity, one hundred books on virology, immunology, the history of science and medicine and related health topics, have attended over fifty-eight AIDS and virology conferences worldwide, have taught thousands of pharmacists in Southern Africa about selenium, and served as an ad hoc consultant to the Ministries of Health of both Zambia and Liberia. I take science seriously and always try to get it right.

            In “The Pandemic” chapter I clearly recognized the echo of  George W. Bush’s Secretary of Defense Donald Rumsfeld with his “known unknowns” and “unknown unknowns”. In your writing I felt you bumping up against the current limits of scientific knowledge. That is when science becomes exciting. Below, I provide a few possible solutions to your unknowns. But first I’ll highlight some sentences and phrases from that chapter.

            “Just when we felt that we knew the cell biology of the  immune system...scientist’s heads were pushed into the lower reaches of hell.” “an autopsy of our knowledge about cell biology is also necessary.” “Hyperactive, dysfunctional inflammation”, “We cannot know the unknown unknowns.” “the pandemic pointed to another gap in our understanding”, “The story we have told ourselves about why SARS-CoV2 is so devious at hijacking our immune systems is, perhaps, a totally incomplete story.” “find only incomplete explanations for phenomena”, “We don’t even know what we don’t know.” “it also exposes gapping fissures in our understanding.” “I cannot think of a scientific moment that has revealed such a deep and fundamental short coming in our knowledge of the biology of a system that we had thought we knew.”

            If I may respond to your expression of scientific exasperation at the limits of our knowledge, I echo your words and reiterate our need to recognize our blind spots and mind the gaps in our understanding. I initially noticed most of that gap in your index - NF-kB, selenium, and antioxidants. Here is my Covid-gap autopsy.

            What did they miss with SARS-CoV2? The same thing they missed with HIV and Ebola. Below are some key missing pieces of the Covid therapeutic and scientific puzzles, both known and unknown unknowns.  

1.      The Env genes of HIV, Ebola, and Covid all genetically encode a selenium containing selenoprotein that forms their viral envelope.

2.      Because of that, rapid viral replication depletes cellular, immune system, and bodily levels of selenium.

3.      Much of cellular selenium is located at the active site of cellular antioxidants.

4.      Viral proteases directly attack cellular antioxidants to release their selenium content for their own use.

5.      Viral destruction of antioxidants damages cellular function, cellular health, and cellular survival.

6.      Depleting the level of selenium in the body causes the thymus to lower production of CD4 cells.

7.      Depletion of CD4 cells causes immune deficiency and dysfunction, and eventually, the cytokine storm.

8.      The NF-kB replication factor affects the level of both inflammation and viral replication.

9.      Nuclear-Factor kappaB inhibitors (NF-kBIs) reduce both inflammation and viral replication.

10.  Thus, anti-inflammatory drugs that inhibit NF-kB act as both anti-inflammatories and antiviral drugs.

11.  More than a dozen steroid and nonsteroid anti-inflammatory drugs exist that could have treated Covid   from the first day of infection, but we mostly used only dexamethasone. (Oncogene (2004) 23:9247-9258). They reduce both inflammation and viral replication.

12.  Rapid viral replication causes rapid depletion of selenium causing CD4 decline and immune collapse.

13.  High doses of selenium - 2.0 mg daily - can help prevent or reverse sepsis and multi-organ-failure.

14.  The essential trace element selenium is the most critical element required for all aspects of immune function. It is concentrated in the cells and organs of the immune system. 

15.  The rapid depletion of selenium and CD4 cell count in severe AIDS, Ebola and Covid-19 that leads to   immune deficiency and dysfunction is the proximate cause of the cytokine storm that leads to the cascade of sepsis, multi-organ-failure, and death.         

 

            I have studied these issues for over thirty years and find that all these pieces of the scientific puzzle fit snugly together. However some say I am wrong. Nevertheless, I believe a close inspection of the known science supports my conclusions because that is where these facts came from. I did not make them up. I just assembled them. In the London Underground the signs read, “Mind the Gap”. We also need to mind the scientific and therapeutic gaps during pandemics or else the next pandemic may not be so kind as Covid-19 was to humanity.    

            I would greatly appreciate your critique of my above theory of the case. I am trying to help close the gap in knowledge to save lives in future pandemics. I have enclosed my book Understanding Covid-19, How 500,000 American Lives Could Have Been Saved. It is a compilation of my Southern African commentaries. I invite you to review the references and excerpts from the scientific journal articles on which I base my analysis. Please turn to pages 156, 231, 366, 372 and 375 for those scientific quotations. .

            Thank you for considering the above proposed gap fillers. For additional context, please find the enclosed copy of my recent letter to Dr Cameron Webb of the White House Office on Pandemic Preparedness and Response. Now I look forward to reading your book The Laws of Medicine as I revise my second book Dear Bill Gates, How to End Serial Pandemic Failure, HIV-1 to Covid-19. 

            Scientifically yours,

            Howard S. Armistead   

            Anti-pandemic Campaigner 

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