This is my ninth entry in my critique of Robert F. Kennedy, Jr.'s book, The Real Anthony Fauci: Bill Gates, Big Pharma, and the Global War on Democracy and Public Health. My first entry is here and you can follow the links from there. Why so many entries, why so many words? It is easy to hurl out lies. Truth-telling takes more time.
A Multitude of Drugs
Two basic problems with this book, as I've already mentioned, are the lack of page numbers and the lack of attaching specific citations at the end of the chapters to specific statements in the book. It seems as though the book was self-published and unedited.
One reason I skip over commenting on some individual claims by Kennedy, is that he makes many remarkable assertions and provides no sources: nothing that matches up to the citation list at the end of the chapters. These include quoting people, statistics, and studies he refers to.
A good example of this begins on page 10 of Chapter One. (I self-numbered the pages out of frustration.) A statement is made regarding the percentage of deaths that occurred in nursing homes. Referring to the citations at the end of the chapter, this corresponds to two references, numbers 45 and 46. Good. Skip over two pages and the next reference that can be attached to the claims about drugs/treatments is on page 13. It refers to the use of hyperbaric chambers in the treatment of COVID. Very specific and matches up to reference numbers, 48 and 49. This leaves at least two pages without any reference beyond number 47 which references the FLCC Alliance, mentioned on page 11.
No references are provided for a multitude of assertions in those two pages, including the effectiveness of many, many compounds that are said to treat COVID. Several of the compounds he has already brought up: hydroxychloroquine, ivermectin, zinc, and vitamin D. Others he lists in a dizzying rap. "Monoclonal antibodies work great" [no they didn't], azithromycin, doxycycline, Celebrex (brand name for celecoxib), bromhexine, NAC (n-acetylcysteine---he also lists "glutathione precursor" which is NAC), IV vitamin C (for God's sake, why stick a needle in someone's arm to give them vitamin C?), quercetin, colchicine (which he strangely capitalizes, he capitalizes several generic drug names), aspirin, fluvoxamine (a pretty serious drug with lots of interactions), and famotidine (he also lists Pepcid separately, a brand of famotidine). These are just the compounds listed before he gets around to providing his next reference, which refers to mouthwashes.
He promotes a whole variety of mouthwashes/nasal irrigants, including povidone iodine, hydrogen peroxide, hypochlorite, Listerine, and cetylpyridinium chloride. He provides a single footnote reference for this which links to an article that asks the question: Did viral rinsing help ASEAN control pandemic or swift action? (an article in the newspaper: India Today) The nasal rinsing study it cites took place in 2019, before COVID.
Some drugs he goes on to name make a limited amount of sense. Dexamethasone had been approved for treating COVID and it is virtually interchangeable in action with the ones he mentions, prednisone, budesonide, and hydrocortisone. (They are also rather toxic and should be reserved for severe cases. One of their toxicities is to lower the immune system. Dexamethasone is chosen because it is longer acting.)
IV Peroxide and Ozone and Other Interventions
This next part comes at the top of a page. As I read it, I thought, I must have skipped ahead as I turned pages. This sounded like satire or else that it must have been introduced with the phrase, "They accuse of us doing ridiculous things like . . ."
Dr. David Brownstein of Detroit. "'We've been treating viral diseases here for twenty-five years, COVID can't be any different.' In all that time, our office had never lost a single patient to flu or flu-like illness. We treated people in their cars with oral vitamins A, C, and D, and iodine. We administered IV solution outside all winter with IV hydrogen peroxide and vitamin C. We'd have them put their butts out the car window and shot them up with intramuscular ozone." (All winter is a strange statement. He published his article in July 2020 and COVID wasn't around for the winter before that.)
IV hydrogen peroxide and intramuscular ozone echo the claim that then President Donald Trump recommended injecting bleach to treat COVID. To be fair, Trump phrased it as a question.
Dr. Brownstein, along with his medical degree, is a graduate of the Desert Institute of Classical Homeopathy. He went on to describe his persecution for his work. "I've been in litigation with the Medical Board for about a year." This is followed by: "In July 2020, Brownstein and his seven colleagues published a peer-reviewed article describing his stellar success with early treatment. FTC sent him a letter warning him to take it down." Brownstein's article is not referenced in Kennedy's citations, but it is not too difficult to find. It was published in Science, Public Health Policy, and The Law, a journal that is directed to health policy rather than clinical studies.
Brownstein described how he obtained his study participants. "For the calendar year of 2020, charts were retrospectively reviewed for the presence of COVID-19 diagnosis occurring from February 2020 through May 2020." February? The first case of COVID-19 in Michigan came on March 10, 2020. Furthermore, he said he retrospectively reviewed charts for his study but also said he had informed consent which, ethically, should have taken place before treatment.
Brownstein alluded to his jabbing the rear ends of his patients through their car windows in his manuscript. "Since we were only treating COVID-19 patients outside the office in the parking lot, intramuscular injections of ozone were deemed the easiest and safest modality."
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| Dr. Brownstein has published several books. Among the uses of ozone therapy he includes cancer, fatigue, infections, autoimmune diseases, and arthritis. |
Kennedy goes on to cite a few more drugs and categories of drugs, mostly without references to support them. This seems to be a general strategy of Kennedy's. He seems to think that dozens of unsupported arguments are more impressive that a small number of supported arguments.
On page 14, Kennedy says, "By that time [fall 2020], more than 200 studies supported treatment with hydroxychloroquine and 60 studies supported ivermectin." He provides no citation to support these numbers. Reviews and meta-analyses of the time don't cite so many studies. This is a good segue to examining ivermectin and hydroxychloroquine.
Let's Look at Ivermectin.
Ivermectin is a great drug for treating certain worm infections. Its discovery was rewarded with a Nobel Prize. At the concentrations used to treat worm infections, it has low toxicity. (Nothing is completely non-toxic.) Let's look at it for treating COVID-19.
Principle #3. Finding compounds that work against viruses is hard. Attacking viruses through pharmacology is difficult.
The whole concept of antiviral therapy is to be toxic to the virus while being much less toxic to the host (e.g., human). This concept is called selective toxicity. Ozone kills viruses. It also kills human cells. Before there were good treatments for AIDS, there were a lot of treatments that had no selective toxicity. One infamous example, taking the blood out of the body and heating it up to the point it killed the virus. That same method also killed the white blood cells which the virus was targeting anyhow. The method was useless.
Viruses are closer to being vectors than living creatures. They are guerilla warriors. They attach to specific human cells, enter them, possess a few mechanisms (through proteins called enzymes) to make more copies of their genetic information and viral shells while plundering the cell's resources (like guerilla raiders), package those copies, and break out of the cell to go on to invade more cells. That provides precious few targets to attack. Most antiviral compounds target the few enzymes the virus uses to make more viruses, or they bind to the virus in the blood (antibodies or vaccines which produce antibodies), or they block entrance into the cell. There are damned few truly good antiviral drugs, that is, those which are effective and which do not have significant toxicities. Ivermectin has been argued to have direct antiviral actions.
To be fair, I should note, that you can contribute to the health of a COVID patient without directly attacking the virus. Vitamin D, by supporting the immune system, does this. Dexamethasone, by lowering inflammation---which can become acute and even fatal during COVID's disease course---is helpful, even though dexamethasone lowers the immune system.
Principle #3a. When it comes to judging a novel therapy, something that has been shown to work in the laboratory seldom works in real life.
Broadly speaking, to prove the effectiveness and safety of a drug, there are three stages: in vitro, preclinical trials (animal), and clinical trials (human). Let's start by looking at ivermectin in the laboratory. In the case of examining drugs that have already been approved, safety studies have mostly been done. In rare situations, using a known drug for a new indication may run into new toxicities. It should also be stressed that, just because safety studies have been done, that doesn't make an approved compound completely safe. Every drug has potential toxicities, some of them have a lot of toxicities.
In vitro, colloquially means showing a drug has an effect in a test tube. More commonly, these experiments take place in well plates. A well plate is an array of tiny depressions. Each well provides an environment to examine a set of conditions. In this setting, testing an antiviral drug requires three ingredients: human cells (which the virus infects), the virus (often at different amounts representing different degrees of exposure), and different concentrations of the treatment being examined. If the treatment works in vitro, the drug rescues the cells from viral damage or death, or else limits or prevents viral growth. At the same time, some wells have the drug (at various concentrations) without the virus to examine to what degree the drug is toxic to the cells. (You can always kill the virus by killing the cells.)
For drugs that work, its effects follow a dose-response relationship: more dose, more response, and hopefully with little to no toxicity at the effective levels. With too little drug there is no effect. With increasing amounts of drug that works you achieve a maximal effect (for example, completely stopping the virus). The response follows a curved line between no effect and maximal effect and from that you can determine the concentration which is effective in inhibiting 50% of the virus.
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| Each "well" is like a tiny test tube. |
Ivermectin has an anti-COVID effect in vitro. This can be seen in the graph below.
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| Ivermectin, in vitro inhibition of COVID-19 (from above cited article). |
From the above graph, several things stand out. One is that the concentration of the drug that inhibits 50% of viral growth (IC50) is 2.8 µM. Secondly, strangely, even 2.0 µM seems to have little effect before a very steep drop.
So, what does 2.8 µM mean? One small problem in interpretation is that these concentrations tend to get reported in two ways in literature, either as µM (or nM) or else by µg/mL (or ng/mL). For ivermectin, the number 2.8 µM is equivalent to 2450 ng/mL.
This study found peak concentrations of ivermectin in plasma to treat worm in infections in humans to be 60 ng/mL. Other studies are summarized here, which compares the worm-treating dose to the COVID-treating dose: "even with the highest reported dose of approximately 1700 µg/kg (i.e., 8.5 times the FDA-approved dose of 200 µg/kg), the maximum plasma concentration was only 0.28µM" (one tenth the dose needed for 50% inhibition).
Or, it could be worse than that. There are aspects of pharmacological effect that are not examined in vitro. Ivermectin has a plasma protein binding of 93.2% (seen in plasma, not in well plates). Therefore, only 6.8% of it is available in its active concentration inside the circulatory system. Even more critical is the intracellular concentration, since the antiviral effect takes place in the cell.
The antiviral effect in humans takes place at a concentration that is forty to several hundred times above its human worm medicine dose. This is consistent with a general truth: in vitro effects rarely carry over to therapeutic effects in humans. Contrary to Kennedy's galloping list of compounds, a good drug is hard to find.
Continued with clinical studies of ivermectin.
Martin Hill Ortiz is the author of several novels including most recently the thriller, Floor 24.
"From the mob underworld to the tops of new skyscrapers, Floor 24 is a heart-thumping New York 1920's historical mystery!" - Holly Newman, bestselling author of A Chance Inquiry mystery series
