On Martin Luther King’s birthday, I traditionally find some sermons I haven’t read yet. In between the birthdays, there are two sermons I keep going back to over and over again: “Loving Your Enemies” and “The Drum Major Instinct.” This passage, in particular, percolates up to the surface of my mind whenever I’m talking to people I passionately disagree with.

The other day I was saying, I always try to do a little converting when I’m in jail. And when we were in jail in Birmingham the other day, the white wardens and all enjoyed coming around the cell to talk about the race problem. And they were showing us where we were so wrong demonstrating. And they were showing us where segregation was so right. And they were showing us where intermarriage was so wrong.

So I would get to preaching, and we would get to talking—calmly, because they wanted to talk about it. And then we got down one day to the point—that was the second or third day—to talk about where they lived, and how much they were earning. And when those brothers told me what they were earning, I said, “Now, you know what? You ought to be marching with us. You’re just as poor as Negroes.”

In case you haven’t guessed from the name of my blog, I’m passionately pro-vax. You might think I’d be disgusted by the fact that some members of my extended family are anti-vaxxers, but I love these family members very deeply. If MLK can call his jailers brothers, then surely I can find love for family members I already love? How hard can these supposedly difficult conversations really be?

However open-hearted I may start off feeling, the vaccine conversations unfortunately have to spend a little effort up front establishing that I’m not the type of scientist who people perceive as an elitist snob that sneers about how deplorably ignorant the unwashed masses are. It’s disheartening that my loved ones start off expecting me to screech at them. Fellow scientists, please! These conversations would be so much easier if we could all make an effort to cut it out with the appearance of sneering. I wish I didn’t have to carefully remind my loved ones that I’m actually the type of scientist who believes valid critiques can come from surprising directions (see: this blog). I’m also the type of scientist who believes that if somebody isn’t understanding my ideas then that’s mostly on me for failing to explain the ideas in terms the listener can understand. Or it might be an indication my ideas are incorrect - a thing that sadly happens quite a lot. Although maybe it’s not so sad. Throwing one bad idea into the recycle bin often makes room for shinier new ideas to take center stage.

In my perception of a typical anti-vaxxer viewpoint, a central animating force is a distrust of institutional scientists. By which I mean scientists who work for Big Pharma, major research institutions, or government regulatory bodies. I’m at least somewhat adjacent to all three of those things at once - but I take great pride in refusing to be tribalistic about it. I certainly wouldn’t say I trust institutions. If that sounds a little tinfoil-hat, then I urge you to watch the brilliant Hulu series Dopesick - which dramatizes the FDA’s approval of disastrously unsupported Big Pharma safety claims for oxycontin. Institutional authorities are conclusively unworthy of blind trust.

Although I can easily understand anti-vaxxer wariness toward institutional scientists, I’m troubled by what I see as credulity toward independent scientists1 and the political podcasters who host them. I strive to adopt the same healthy skepticism toward independent scientists that I apply to institutional scientists.

Which brings us to vaccine beer. I was forced to temporarily take off my institutional scientist hat to develop vaccine beer as an independent scientist. My institutional colleagues urged me not to follow this disobedient path, because we all know the FDA/Big Pharma track is the only respectable way to develop vaccines. When I told one colleague about the idea that vaccines could be dietary supplements, he asked “why would you want to get in bed with those assholes?” I gently reminded him that some of the assholes might sometimes be making valid points. We then proceeded to develop a list of the dietary supplement products the colleague swears by.

From my vantage point, institutional scientists typically put too much faith in institutional authority, while being too casual in their dismissal of all independent scientists as dangerous snake oil salesmen. We really gotta work on this sneering problem.

The vaccine skeptics I’ve talked to so far seem pretty interested in vaccine beer, so long as I reassure them I’m not trying to slip it into their tap water2. For that part of the discussion, it helps to note that our institutional research paper shows manufacturers how to turn the vaccine yeast a lurid hot pink. It’s not exactly what a moustache-twirling Institutional Scientist would do if he were trying to secretly sneak something into the food supply.

The issue at the base of this post is that my loved ones love me too - so they’re hardly offering me a representative view of what strangers might think about vaccine beer. Hearing other viewpoints might help us figure out how to quickly make vaccine beer a mass-market reality. If anybody’s at a family gathering with vaccine skeptics this holiday season, you’d be doing me a huge favor if you can channel your inner MLK and ask - in as loving and open-hearted a fashion as you possibly can - to hear more about their thinking. It should ideally be more like neutral sociology research than an attempt to screech any sort of vaccine gospel.

Alternatively, you could invite vaccine skeptic friends to please directly post some comments here on this blog. I really mean it about trying my very best to implement MLK’s teaching that it’s healthier for me to love my alleged so-called enemies. Read the sermon. It might convince you too3.

Song of the day:

The country needs and, unless I mistake its temper, the country demands bold, persistent experimentation. It is common sense to take a method and try it: if it fails, admit it frankly and try another. But above all, try something. The millions who are in want will not stand by silently forever while the things to satisfy their needs are within easy reach.

-Franklin D. Roosevelt, 1932 presidential campaign

In prior posts, I’ve attempted to coin the verb “tuskegee” to describe the disastrous decision to withhold medicine from a person who needs it. Unfortunately, the word tuskegee turns out to be about as popular at parties as a turd in the punchbowl. It lands in people’s minds solely as a screech of raaaacism[clutch pearls], and it takes a lot of effort to explain why the Tuskegee Study is also a story about physicians blithely refusing to treat a deadly disease.

Another problem with the verb tuskegee is that it’s not really broad enough. Withholding medicine is only one of a wide range of scenarios where refusing to take action could get somebody killed. It would be strange to call this classic Don’t Look Up scene, in which a president refuses to take action to avert a disaster, “tuskegeeistic” - even though it kind of is:

Proposal

The central claim of this article is that there is a general human mental bias toward inaction, even when inaction obviously isn’t the best available option. This bias makes it harder for individuals and institutions to weigh the risks and benefits of various possible actions against the risk that an unaddressed status quo will lead to disaster.

Neologism

In the magic-suffused world of Ursula LeGuin’s Earthsea novels, knowing the secret “true name” of a thing grants a wizard the power to command the thing. LeGuin is playing with the idea that having a precise term for something helps you recognize, understand, and ultimately control its deeper nature. Having a word for situations where inaction causes a preventable disaster might give us more power over the problem.

English has a rich vocabulary for regrettable actions. For example, a debacle is what happens when somebody takes actions that precipitate an embarrassing fiasco they should have seen coming. Napoleon’s attempt to break the battle line at Waterloo was a classic debacle. In contrast, we don’t have succinct terms for describing undesirable outcomes that happen because somebody failed to take sensible action. I therefore propose:

Dis•action - when refusal to take action in the face of an identifiable risk leads to predictably undesirable consequences

The neologism unites the root word dis- (“not” or “separated from”) with action. Alternatively, it could be inferred as a portmanteau of “dis-inaction,” where dis- denotes “ill” (as in the familiar word disaster, which derives from “ill-starred”).

In some situations, inaction might obviously be the wisest available bet. An antonym for disaction could be “euaction” - a portmanteau of eu- (“well” or “good”) and inaction.

In The March of Folly, Barbara Tuchman defines “folly” as policies pursued by governments that run against their own self‑interest, where other feasible courses were available and known, and where contemporaries recognized and warned that the chosen course of action was counterproductive. We’re essentially proposing a special sub-category of Tuchman’s “folly,” in which bias against the perception of a looming disaction ends in disaster.

Terms that can help illuminate how disaction bias creeps up on us

Omission bias. Psychological experiments have shown that people tend to judge harmful actions more harshly than equally harmful omissions of action. Individuals and, in particular, bureaucracies are intuitively aware of omission bias - so inaction tends to be judged as reputationally “safer” than any given action, even in cases where inaction obviously is not the safest choice.

Risk-inflation. Inflating perceived risks for various actions while downplaying the risks of doing nothing. The classic example here is Golden Rice - a GMO rice strain that produces beta carotene (a harmless dimer of vitamin A). Entities like Greenpeace hysterically whipped up the imaginary risks of Frankenstein environmental disasters while discounting the benefits of treating vitamin A deficiency in low-income countries. Our collective disaction on Golden Rice killed more kids than the Nazis.

Futility bias. There’s a human mental bug where the likelihood of an action actually working is inappropriately discounted. Futility bias tilts the scales toward inaction. An example of this bias is NASA’s abject failure to try to do DNA deep-sequencing samples from Mars and the asteroid Bennu.

Vetocracy. The classic example here is the liberum veto of the 18th century Polish-Lithuanian Commonwealth. The idea was that since all the noblemen in Parliament were equal, they should all have an equal right to object and suspend lawmaking. Pretty soon, Russia figured out that all they had to do was bribe one dirtbag and the Polish Parliament would be left lying flat on its back doing nothing. Poland was carved up and dissolved at the end of the 18th century.

Status display. Bold proposals by underlings are rejected because they are seen as a disrespectful challenge to authority. This mechanism typically employs credentialism and appeal to authority fallacy. It often intersects with failures of imagination.

Failure of imagination. I’ve been drifting in and out of obsession with the third interstellar object, Atlas. Its strange behaviors demand the use of a full range of space telescopes, but because NASA sees speculation as taboo they’ve decided not to use some of the telescopes that could rule out some of the more exotic hypotheses independent scientists have been dreaming up on Medium. And no, I’m not talking about aliens. My hypothesis for the past four months has been that Atlas might have a magnetic field and a thin oxygen-nitrogen atmosphere. The atmosphere can be ruled out with far-ultraviolet imaging. The failure of imagination at NASA means they’re disactively still not using any of the far-UV telescopes.

Decorousness. Respect for norms and taboos - and a reluctance to rock the boat. Merrick Garland, the worst law enforcement attorney in human history, is the poster child for this insidious greased skid toward disaction.

Laziness. There’s sometimes an element of laziness underlying futility bias, but at a general overview level I don’t think being lazy is usually a direct factor underlying the folly of disaction. Disasters that arise from laziness are basically just dereliction of duty - we already have plenty of existing words for that type of thing.

Future posts

My brother Andrew’s critique of an early draft of this post was that it seemed like I was arbitrarily lumping together all the different topics that are currently annoying me. There’s a grain of truth in this critique, but I would reframe it more charitably as a sudden realization that there’s a hidden thread tying together many of the ideas I’m currently wrestling with. Now that I have a word for the phenomenon, I’m seeing it all over the place. In bullet points:

•I’ve taken to calling the bioethics committees at work the disactionista brigade. But only after my husband, , scolded me for calling them disactionazis.

•I’m going to hand off future posts covering disactive episodes in history to my history-nerd husband.

•I’m interested in ecology and the environment (even though I don’t post about it much), and it has been dawning on me that whole subject area is awash in disactional thinking.

•The US housing market is a disactionist disaster area. The political faction that most desperately needs this neologism is the Abundance crowd. Government-enforced disaction is the exact thing they’re annoyed by.

Stay tuned!

Song of the day: Sometimes disaction stems from the fear that you’re not equipped to take the needed action. Maybe “cowardice” belongs on the disaction-associated terminology list.

In this post, I’m mirroring the independent manuscript I wrote describing my home experiments. There’s also an institutional manuscript showing that drinking beer made with vaccine yeast induced a strong antibody response in me. Tina Saey’s excellent coverage of the controversies surrounding the new tech can be found here.

In the near future, I hope to convince major brewing yeast suppliers to start offering “vac yeast” for microbrewers and homebrewers to play with. While we wait for that to happen, it’s already possible for independent scientists to try all this stuff at home, exactly as I did.

The Supplemental section of the posted manuscript contains a wealth of technical detail about our methods for homebrewing and drinking vac beer. Unfortunately, the detailed methods too long for the blogging platforms, so I’ll simply direct interested readers to the Zenodo posting.

The appendices of the home experiment manuscript are given separate coverage here and here.

Vaccine Beer: A Personal Healthcare Report (v.2)

Christopher B. Buck

Independent Scientist, Bethesda, Maryland, USA

Abstract

Recent results suggest that live yeast expressing vaccine antigens can elicit an immune response in mice when delivered in the form of food. In this study, I conduct an n-of-1 self-experiment to explore the idea that the mouse results can safely be extended to myself. I reasoned that the experiment stands a good chance of serving my own general health interests. I bioengineered brewer’s yeast to express the BK polyomavirus major capsid protein as a model vaccine antigen. I then used the yeast to homebrew beer. Drinking prime and boost doses of the bioengineered yeast did not cause any discernible adverse effects. The results demonstrate that food manufacturers and home cooks can independently explore the development of food-based vaccines in a basic kitchen environment.

Introduction

In common parlance, the familiar term “vaccine” refers to a class of medical products that are intended to prevent and treat infectious disease. While it’s true that all commercial vaccines that might be recommended at a routine physical are FDA-approved drugs that have been proven safe and effective, these familiar products are only one aspect of the scientific usage of the term vaccine. For example, here is a scientific definition from the National Cancer Institute (NCI):

Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

The definition focuses on the ability of the vaccine to elicit an immune response, regardless of whether the immune response is intended to prevent or treat disease in the recipient. Research scientists often investigate the effects of antiviral vaccines on the function of the immune system using model animals that cannot be infected by the target virus (Soleymani et al., 2025). In other cases, vaccines are used to support innate immune responses that are not specific to any particular pathogen (Zhang et al., 2026). These cases demonstrate that the purpose of applying a vaccine is not always to prevent a specific disease in the vaccinated individual. In other words, the scientific definition of the word vaccine simply denotes the intent to elicit an immune response against an antigenic target and does not necessarily imply a disease-prevention intent for the recipient.

Findings from an NCI team show that food-grade brewer’s yeast expressing the coat protein of BK polyomavirus (BKV) can be immunogenic when fed to lab mice (Soleymani et al., 2025). The results are exciting because food-based vaccine approaches are fast and cheap to develop. More importantly, food products can immediately be marketed with the intent of supporting the normal healthy structure and function of the human body (21 U.S.C. § 321(g)(1)).

In this report, I explore the idea that the NCI’s food-based vaccine strategy can be safely extended to humans. My approach follows the centuries-old tradition in which vaccine scientists voluntarily test initial products on themselves (Contagion, 2011; Hanley et al., 2019; Weisse, 2012). The purpose of the study is to confirm the predicted safety of food-grade bioengineered BKV yeast and to investigate whether the yeast elicit an immune response. The self-experiment was conducted in my home kitchen using only my own personal resources as a private citizen.

Although I am not at risk of any known BKV diseases, I entertain the hope that the immune responses I might experience during the study could benefit my general health. I aim for this to be the beginning of a movement to democratize vaccine development by making the process freely accessible to individual citizens (Jain, 2025; Kraushaar, 2024; Mastroianni, 2023).

Materials and Methods

Ethics statement. In my view, scientific self-experimentation in service of individual healthcare is a fundamental human right (C. Buck, 2022; C. B. Buck, 2023). My viewpoint rests on a long tradition of scientists ethically testing research findings on themselves and is supported by the Nuremberg Code, which explicitly allows for the possibility of ethical self-experimentation (Hanley et al., 2019; Sills et al., 2020). The right is self-evident under the ethical Principle of Autonomy (Childress, 1990; Gauthier, 1993). Detailed reasoning on this issue is presented in Appendices A and B.

The independent generation, consumption, and sale of bioengineered organisms is allowed under US law (Kramer, 2023). In my view, the bioengineered yeast described in this report satisfy self-asserted Generally Recognized as Safe (GRAS) food standards (FDA, 2017). Detailed reasoning on this issue is presented in Appendix C.

The individual healthcare activities documented in this report did not use any confidential information, did not use or generate any intellectual property, did not generate any revenue or equity, and did not solicit, receive, or use any government resources. The self-experiments were conducted in a home environment outside of work hours and do not in any way invoke my professional titles. This report does not provide any professional services and does not endorse any persons, entities, or products.

Plasmid construction. The sequence of pGustiv was downloaded from the NCI Lab of Cellular Oncology’s public technical page. The sequence was synthesized as a set of cloned fragments by GeneUniversal.com. Fragments were recombined in a home lab setting using traditional restriction enzyme-based cloning methods (NEB.com). Scientific equipment was purchased from The-Odin.com or via Amazon.com. The finished pGustiv plasmid is publicly available for any purpose, including human studies or commercial purposes, under OpenMTA (Kahl et al., 2018) via Addgene.org. I note that various companies, including Gene Universal, offer custom cloning services that would obviate the need for home laboratory equipment.

Yeast transformation. Detailed methods for transforming yeast and producing beer are provided in the Supplemental Methods section of Version 1 of this preprint. In addition, I note that many companies, including Gene Universal, offer yeast transformation services.

Yeast strains of interest were transformed with pGustiv using a yeast transformation kit (The-Odin.com) and selected on YPD-agar plates (KDmedical.com) with 6 mM formaldehyde (SigmaAldrich.com). Six colonies were pooled into liquid YPD with 6 mM formaldehyde (YPD-6) and cultured with orbital shaking at 30ºC for several hours prior to streaking onto malt extract plates (OlympusMyco.com). Six of the largest and most fluorescent colonies were picked into 250 µl of YPD-6 and cultured overnight. The culture was then progressively stepped up to 25 mL and 250 mL of YPD-6 in stirred Erlenmeyer flasks.

Beer. Detailed methods for production of initial homebrewed batches of transformed yeast are provided in the Supplemental Methods section of Version 1 of this preprint. Simplified methods used for later batches of yeast are provided in Appendix D (below).

Yeast cells from a 250 mL flask were centrifuged (LabFish.com) at 650 x g and the YPD-6 supernatant was discarded. Collected yeast cells were pitched into one liter (~one quart) of 1x Propper starter broth (OmegaYeast.com) in a 5-liter (~one gallon) continuous brewing jar (CulturesForHealth.com). The starter was cultured on a heated stir plate until expression of the green fluorescent protein (GFP) marker gene started to become evident, roughly 6-12 hours. Three liters (~3 quarts) of filtered tap water and 0.5 kg (~1 pound) of dry malt extract from a MoreBeer.com Flash Hefeweizen kit were added to the fermenter. Thirty grams (~1 ounce) of Saphir hop pellets (Artisan Hops) were steeped in a French press (Frieling.com) in 0.5 L (~1 pint) of boiling water. The hop tea was cooled and pressed and the filtrate was added to the fermenter. Fermentation was conducted at 24 to 34ºC (75-93ºF), depending on yeast strain.

The home kitchen environment did not have the resources to quantitate VP1 dosing, but a rough estimate would be that, indexed to body mass, I consumed roughly 1/38th of a mouse dose of induced live yeast during each roughly five-day dosing window.

Self-experiments. I conducted pilot self-experiments by consuming yeast on an arbitrary “best guess” convenience schedule consisting of one or two pints (0.5 L) of beer per day.

Robust GFP expression was observed in the fermenting beer starting roughly 36 hours after pitching, at which point a pint of fresh beer with suspended live yeast was decanted from the stirred fermenter and immediately consumed at fermentation temperature. At day 3 of the fermentation, the remaining beer was distributed into one-pint flip-top bottles and carbonated by the addition of 1% (w/v) maltose (LabAlley.com).

Detailed methods for production of foods consumed alongside the vaccine beer are presented in the Supplemental Methods section of Version 1 of this preprint. In brief, a 20 mg dose of famotidine was taken about an hour in advance of some pints, in hope of partially neutralizing stomach pH to promote the survival of live yeast. Sugar-free calcium carbonate antacid tablets were chewed alongside some meals, with the same rationale. In some cases, a pint of water was consumed about ten minutes prior to drinking the pint of beer, in hope of rinsing stomach acid into the duodenum. Some pints were consumed on an empty stomach, while others were consumed alongside maltose-rich foods, in hope of achieving prebiotic yeast-feeding effects. Some of the pints were consumed together with a high-fat meal, exploring the idea that the secretion of bile salts might help promote yeast lysis and release of BKV VLPs in the duodenum. In summary, the prime and boost dosing schedules consisted of one or two pints of vaccine beer per day over the course of about five days.

Results

The traditional Uniform Biological Material Transfer Agreement (UBMTA) used by the NCI team stipulates that transferred materials cannot be used in human subjects. The UBMTA also forbids further sharing or resale of transferred materials. It was therefore necessary to independently recreate the pGustiv sequence reported by the NCI through de novo DNA synthesis. Plasmid construction was conducted in my home kitchen. The finished plasmid is freely available via Addgene under OpenMTA, which allows for use in humans and commercial resale (Kahl et al., 2018).

The pGustiv plasmid was initially transformed into Pakruojis Lithuanian Farmhouse Ale Yeast (WLP4047) in my home kitchen. The transformed yeast strain was used to brew batches of roughly a gallon (4 L) of beer. I drank one or two pints (0.5-1 L) of the resulting vaccine beer per day over the course of about a week (Figure 1).

The wheat ale yeast strain (WB-06) that comes with the Morebeer Flash Hefeweizen kit also produces a flavorful live-yeast beer. Results from the NCI team suggest that the wheat ale strain may exhibit somewhat higher and more stable vaccine antigen expression than the Pakruojis strain. I drank booster doses of vaccine beer made with the wheat ale strain starting at roughly week seven after the Pakruojis priming doses. A second round of booster doses using WB-06 beer was consumed about seven weeks later.

The NCI team’s vaccination experiments with mice suggest that it’s important for live yeast to shuttle the fragile vaccine antigen past the stomach acid barrier. I suspect it’s also important for the yeast cells to eventually break open and release the antigen so it can directly bind the surface of specialized immune presentation cells called M cells in the small intestine (de Aizpurua & Russell-Jones, 1988). I have entertained multiple hypotheses about which foods might be most effective for facilitating these processes. I don’t know which, if any, of the hypotheses are true, and some of the hypotheses are mutually exclusive. I adopted a bet-hedging strategy in which I implemented different strategies on different days.

In healthy individuals, yeast can persist in the gut for periods of up to a few days (Pecquet et al., 1991). One hypothesis is that it might be possible to restimulate antigen expression in yeast residing in the small intestine. The MAL32 promoter system used in pGustiv is activated by maltose, so eating maltose-rich foods might restimulate antigen expression. A complicating factor is that glucose suppresses the MAL32 promoter, even in the presence of high levels of maltose (Meurer et al., 2017). In essence, yeast cells are set up to utilize glucose as a preferred “snack food” before they activate the machinery to metabolize other sugars, such as maltose.

In pilot self-experiments, eating maltose-rich/low-glucose foods alongside vaccine beer sometimes correlated with mild bloating and flatulence, reminiscent of the familiar effects of eating beans. I also considered the hypothesis that gut fermentation might produce ethanol at levels that could produce inebriating effects beyond what might be expected from drinking a pint of beer. I did not sense any signs of ethanol intoxication during the experiments. This is consistent with the idea that so-called “autobrewery” effects are extremely rare and are typically associated with microbes unrelated to the Saccharomyces cerevisiae used in this study (Hsu & Schnabl, 2026). No other discernible side effects were detected at any point during or after the experiments.

Before and after drinking vaccine beer, I collected serum samples from myself via fingerstick. I established a non-equity non-profit recreational organization, Gusteaucorp.org, to serve as a public repository for my own serum samples. Repository samples were shared with the NCI team at no cost, with an invitation to test the samples for serum antibodies specific for BKV VP1. The results of the testing are reported in a separate NCI-led manuscript (Soleymani et al., 2025).

Discussion

There is an urgent need to find ways to make vaccine development faster, cheaper, easier, and more broadly accessible. Food-based vaccine approaches can achieve these goals.

In the United States, there has been a growing movement to downplay the safety and efficacy of traditional injection vaccines, and government officials have begun implementing policies restricting access (O’Reilly, 2025). Food-based vaccine approaches could help put autonomous decision-making authority back in the hands of individual Americans. Homemade vaccines might also help overcome some of the skepticism and fear surrounding injected vaccines developed by pharmaceutical conglomerates.

The existing regulatory framework in the US empowers food producers to sell innovative new products. For example, a number of companies have developed bioengineered brewer’s yeast strains that express enzymes intended to make beer more flavorful (Kramer, 2023). Other yeast-based food products have been tested for their ability to support the normal healthy structure and function of the immune system (Jensen et al., 2011; McFarlin et al., 2023; Moreno et al., 2025; Roos et al., 2018). Food-grade yeast carrying vaccine antigens of interest are a new entrant in this fascinating segment of the American food market.

Colleagues have expressed the concern that because vaccines are typically considered drugs, potentially antigenic bioengineered yeast should only be developed under the authority of the FDA drug approval process. This concern overlooks the fact that foods can have healthful properties without being considered drugs. Limes, which have long been used to prevent and cure scurvy, are a classic example. If a modern farmer were to label limes with the stated intent of curing scurvy, the labeled limes would be subject to the authority of the FDA drug approval process. The reverse is not true. The fact that limes can be used to cure disease does not mean limes can no longer be marketed as food. The law focuses on manufacturer intent, as reflected by product marketing literature. Food-based vaccines can occupy the same market space as limes, so long as the food-vaccine product focuses only on structure-function effects and refrains from making claims about disease. Detailed reasoning on these issues is presented in Appendices A-C.

Evaluation of the possible medical efficacy of food-based vaccine strategies will be an important future aim that can be conducted under FDA investigational new drug applications. Meanwhile, consumers are free to immediately begin exploring this exciting new class of food products (C. Buck, 2025a, 2025b, 2025c).

Disclosures

I am employed by the National Cancer Institute (NCI), where I am a member of a team developing food-based vaccine technology. The results and ideas presented in this report exclusively represent my personal identity as a private citizen and do not represent my views as a federal employee or the official views of NCI. This study was conducted as a personal health activity during my free time and did not use any government resources.

References

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Foods can be vaccines. It’s an exciting idea at a basic scientific level, but the best part is that it means vaccines can be regulated as foods. It means vaccine development can be democratized. In the inspirational words of Chef Gusteau in the movie Ratatouille:

Great cooking is not for the faint of heart. You must be imaginative! You must try things that may not work. You must not let anyone define your limits because of where you come from. What I say is true: anyone can cook. But only the fearless can be great.

The first objection I hear from some scientific colleagues comes along the lines of “you’re not fooling anyone with this food thing - we all know vaccines are drugs.” While it’s true that all previous vaccines have been marketed with the intent of preventing disease - a regulatory bright line that makes them drugs - that doesn’t mean that all future vaccines can only be considered drugs.

My colleagues are missing the point made in my carrageenan post, where I illustrate the fact that a given ingredient can simultaneously exist as a food in some products and a drug in other products. Another example is artemisinin, which is separately marketed either as an FDA-approved anti-malarial drug or as a food supplement product. We all know artemisinin is a drug, but that doesn’t mean it can’t also be a food. A third example is vitamin C - that fact that it exists as an FDA-approved injection drug used for treating scurvy doesn’t automatically turn limes and multivitamins into drugs.

The bright line is that food products only become drugs if the manufacturer makes marketing claims indicating that the product is intended to prevent or treat disease. Foods can be advertised as having general effects on normal healthy bodily structures and functions, they just can’t be advertised with the intent of treating disease.

An important point is that the food versus drug distinction is focused on manufacturer intent, as revealed by marketing claims. At the consumer level, people are free to read medical literature and choose foods they hope might treat a specific disease. If you know you have vitamin A deficiency, you’re allowed to go buy some carrots with the explicit intent of curing yourself of the disease. You could also choose to eat Golden Rice (a food product intentionally engineered to provide vitamin A). The law also allows physicians and scientists to advise patients and the general public that carrots and Golden Rice are known cures for vitamin A deficiency. At a marketing level, it’s only the manufacturer whose hands are tied.

In the Discussion section of our vaccine beer manuscript, we draw an analogy to spinach - which contains an Investigational New Drug (IND) called zeaxanthin. If you wanted to test the hypothesis that the zeaxanthin in spinach can prevent a form of blindness called macular degeneration (which extensive scientific literature suggests is possible) you would need to alert the FDA with an IND application before your spinach product could go into controlled clinical trials. The IND filing would make the specific spinach product being used in the clinical trial a not-yet-approved drug. Spinach on supermarket shelves would still just be spinach. A food manufacturer could also lawfully sell a GMO spinach strain engineered to have ten times more zeaxanthin [1], so long as the super-spinach food product doesn’t carry the marketing claim that the added zeaxanthin is intended to prevent macular degeneration. The point is that foods - including foods with ingredients known to have possible disease-fighting effects - are regulated differently than drugs.

A challenging marketing question is whether the word “vaccine,” all by itself, can only be construed as an intent to prevent or treat disease. The Merriam-Webster’s definition of the word vaccine describes a methodology that can have various possible intents:

A preparation that is administered (as by injection) to stimulate the body's immune response against a specific infectious agent or disease.

A definition from the National Cancer Institute also describes multiple possible intents:

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

The word “or” in the definitions highlights the fact that infectious agents aren’t the only possible target for vaccines, and it highlights the fact that infectious agents aren’t necessarily synonymous with disease. Viruses often cause disease, but infections can also be asymptomatic. In the case of the BK polyomavirus (BKV) vaccine beer [2] I drank, my consumer intent reflected a hope for general health benefits. Although BKV infection is widely described in scientific literature as “asymptomatic” or “harmless” in healthy individuals, the virus can sometimes cause diseases of the kidneys, bladder, gut, brain, and cardiovascular system in immunosuppressed people. I also worry that BKV may be modifying normal bodily structure/function in other ways we simply haven’t figured out yet. The BKV vaccine project was essentially just a philosophical “no thanks” to BKV as a general health proposition - as opposed to a specific intent to prevent or treat any particular disease. It could be broadly described as a way of supporting the normal healthy functions of my immune system. This is a general-health structure/function claim can be found on approximately 25,000 food product labels.

In summary, having the term “BKV vaccine” on the label isn’t claiming an intent for therapeutic efficacy for any particular disease - the intent is simply to inform consumers about the presence of a specific component of the food product that could have possible health effects (including hypothetical hazards). It’s no different from telling people limes contain vitamin C.

In the vaccine beer manuscript, we report the first commercial sales food-grade vaccine-yeast products. The starting goal wasn’t to be scalable or profitable - the major initial aim is to satisfy specific aspects of food and drug law. As described in detail in Appendix B (reproduced verbatim below), if the first appearance of a substance is on the FDA IND track then it can never later be marketed as a food supplement product - it can only ever be considered a drug. The initial sales of the yeast as a food (to a set of customers with expertise in vaccine design) secures its status as a product that any company can sell as a general health food product even if, in parallel, it goes through clinical trials as a possible disease-preventing drug in the future.

When I imagine future sales to less expert customers, I start to worry that omitting the word “vaccine” from the product label could make some consumers think we’re trying to furtively sneak vaccines into the food supply. That’s the exact opposite of what we’re trying to do. The goal of this work is to promote open source vaccine development in a way that will increase everybody’s freedom of choice. Tricking people into doing things absolutely is not on the agenda.

The fact that the word vaccine is intended to describe an ingredient can be emphasized by referring to the emerging product category, in general, as “vac-foods” — where vac stands for “vaccine antigen-containing.” The possible vaccine antigen would be listed as a bioengineered component of the food product. My sense is that this compromise approach should be readily intelligible to consumers, while also lowering the hackles of scientific colleagues and regulators. We all know that familiar vaccines are drugs, but maybe we can all agree that vac-foods are foods [3].

This is a controversial new area of legal interpretation, and I’m not a lawyer. Comments - especially constructive criticism or cautions - are most welcome [4].

Footnotes

[1] GMO tomatoes engineered to produce a class of drugs called anthocyanins are marketed as a food with a range of possible general health benefits.

[2] Grapes, apples, and honey don’t have enough maltose to trigger the production of the vaccine antigen. All you beer-haters out there will have to develop your own expression systems. Or you could learn to love beer? It built the pyramids! How bad could it be.

[3] In the surprising event that courts eventually rule the category name “Vac-Yeast” an impermissible disease claim, manufacturers could resort to a category name like “Immune Support Yeast” (with the expressed antigen simply listed as a bioengineered component). I like this market approach a lot less, because it risks tricking consumers into accidentally drinking vaccines. But it’s good to know there’s technically a backup plan that only uses a permissible general health structure/function claim.

[4] In response to reader comments, I extensively revised this post several times during the last week of December 2025 and again in April 2026. Thanks, readers!

Song of the day: With apologies to Uncle Byron, who didn’t like war metaphors, I say again: Viruses. Must. Die.

Appendix B. Food structure-function studies do not require IND

This study does not require an Investigational New Drug (IND) application because it is an investigation of the effects of a food on the normal healthy structure and function of the human body, which is explicitly allowed under 21 U.S.C. § 321(g)(1)

(g)(1) The term “drug” means (A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C). A food or dietary supplement for which a claim, subject to sections 343(r)(1)(B) and 343(r)(3) of this title or sections 343(r)(1)(B) and 343(r)(5)(D) of this title, is made in accordance with the requirements of section 343(r) of this title is not a drug solely because the label or the labeling contains such a claim. A food, dietary ingredient, or dietary supplement for which a truthful and not misleading statement is made in accordance with section 343(r)(6)* of this title is not a drug under clause (C) solely because the label or the labeling contains such a statement.

*343(r)(6) a statement for a dietary supplement may be made if the statement… characterizes the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function, or describes general well-being from consumption of a nutrient or dietary ingredient

The statutory definition indicates that a food can be intended to affect the structure and function of the body without being considered a drug, so long as the food is not intended to prevent or treat disease. I do not have, and I am not at risk of developing, any of the diseases BK polyomavirus is known to cause. The stated intent of the self-experiment was not to study disease, but rather to measure the effects of a food on the normal healthy structure and function of my immune system.

The scientific literature includes many examples of IRB-approved clinical investigations evaluating the effects of yeast-based food products on the structure and function of the human immune system, including measurements of virus-specific serum antibody responses (Jensen et al., 2011; McFarlin et al., 2023; Moreno et al., 2025; Roos et al., 2018). Investigations of this type are never conducted under IND because they are food studies, not drug studies.

I’ve never visited a sex worker. I don’t have major moral objections to the practice, but nature conveniently built me with an overwhelming inclination toward strict monogamy - and my marriage is coming up on 30 years.

If something changes and I decide to start having sex with strangers, I’ll apply all of my professional research findings to my outside activities. I’d get a dose of the updated Gardasil-9 HPV vaccine, I’d ask my doctor for HPV DNA testing at my annual physical, I’d go on PrEP, and for good measure I would slather myself with a sex lube that uses a food-grade seaweed extract called carrageenan as the principal gelling agent1. Here’s the relevant paragraph from my 2006 publication:

Some, but not all, carrageenan-containing over-the-counter sexual lubricant gels we tested were extremely effective for blocking the infectivity of an HPV16 reporter pseudovirus in vitro. These results raise the possibility that use of such lubricant products, or condoms lubricated with carrageenan-based gels, could block the sexual transmission of HPV. However, in the absence of clinical efficacy data, it would be inappropriate to recommend currently available products for use as topical microbicides.

After my recent experiences with vaccine beer, it makes me cringe to read my own words. I now realize it is highly appropriate to recommend that people consider using carrageenan lube as a possible way of defending themselves against HPV.

Seventeen years after my initial discovery, an FDA-supervised randomized controlled drug trial confirmed that carrageenan is safe and at least somewhat effective for preventing HPV infection. In parallel, carrageenan also remains on the market as a generally recognized as safe (GRAS) food and cosmetic ingredient. In other words, carrageenan simultaneously exists both as an FDA-compliant food ingredient and also as a candidate for FDA drug approval. Which of the two categories a given carrageenan product occupies is dictated solely by whether any disease claims are printed on its label.

While we wait for FDA drug approval, it is ethically sound for physicians and scientists to tell people about scientific results indicating the type of health effects various food and cosmetic products might plausibly be expected to have, even before possible risks and benefits are conclusively proven. In fact, it would be unethical to obscure such useful scientific knowledge from public view.

I hereby apologize for my inappropriate use of the word inappropriate. As penance, I am appropriately recommending that, if you sleep with strangers, you should consider using a currently available carrageenan lube product. Because why the hell not.

Song of the day: I’m a strict monogamist, but I’ll confess to sometimes harboring crushes.

The term “self-care” gets a bad rap. My AI defines it as:

The ability to care for oneself through awareness, self-control, and self-reliance to achieve, maintain, or promote optimal health and well-being.

That sounds great, but if I follow up with the prompt “are there derisive meanings” I get:

Self-care is sometimes mocked as code for pampering, consumerism, and “treating yourself” (e.g., spa days, expensive products) rather than substantive efforts to improve health or functioning.

I confess that when I free-associate self-care the first thing that comes to mind is Goop. I’m not a subscriber.

The basic problem with the term self-care is the same as the problem with science in general. Science is a strong-link problem, not a weak-link problem. The scientific method gives us a way to identify strong links that don’t break under experimental testing. The trouble is the strong links are often hidden under an immense pile of weak links. It’s the classic “diamonds in a dung heap” formulation that Thomas Jefferson used to describe his efforts to find wisdom in the Bible.

In short, the existence of lots of useless crap in the self-care arena absolutely does not mean that everything in the arena is crap. Careful use of the scientific method can help us sort out the diamonds. By which I mean developing hypotheses that comport with available evidence and then doing experiments that test the hypotheses. Here, Thomas Jefferson missed a diamond. When the Declaration of Independence talked about unalienable Rights, it should have said, “Life, Liberty, and the pursuit of Experiments.”

All this may sound so obvious it doesn’t warrant spelling out, but this week I’ve been wrestling with the fact that an institutional ethics committee rejected a self-care proposal in which I would bring vaccine yeast home from the lab, brew beer with it, and then prick my own finger to see if I developed any antibodies. After the institutional veto, I resorted to setting up a shoestring molecular biology lab at home, re-creating the needed yeast using only my own personal resources, and drinking vaccine beer in the comfort of my kitchen. To my surprise, the ethics committee is now arguing that because the kitchen self-care experiment is scientifically “related” to my official duties it should be viewed as unauthorized human subjects research - a form of misconduct that can be grounds for termination.

The idea that an institution might have the legal authority to veto “work-related” menu planning in an employee’s home kitchen is prima facie ridiculous. How did we get into a situation where an ethics committee thinks this argument sounds even remotely reasonable?

My brother and I struggled mightily with this question when writing up our home vaccine beer projects. We think the answer boils down to a badly written section of a law called the Common Rule. After huge amounts of email and Facetime back-and-forth (my brother and I love to debate) we hammered out Appendix A - which presents our considered layman’s analysis of the Common Rule and the history behind it. I guess Appendix A comes off as a little bit stiff and scattered - you can kind of tell it was written by committee. I’ll reproduce the scholarly text in its entirety in the footer, but up here in the main post I’ll try to briefly summarize my individual view of the controversy in more conversational terms.

For anybody who’s unfamiliar with the concept of an Institutional Review Board (IRB), I recommend ’s epic tale, “My IRB Nightmare.” Even for people who are familiar with IRBs, Alexander’s classic post can help emphasize the point that the nightmare I’m describing here isn’t unique.

The basic idea behind the Common Rule is that if scientists are allowed to do whatever experiments we want then some of us might prioritize our own research interests over the individual best interests of study volunteers. A scary thing is that abuse of study subjects can be accidental - a scientist might simply fail to adequately inform study subjects about risks, leaving subjects poorly equipped to defend their own individual interests. It’s a serviceable description of what happened in the insidious Tuskegee Study of Untreated Syphilis - where scientists quietly withheld penicillin from black men with latent syphilis. The Common Rule addresses a real and very serious problem by applying the entirely reasonable approach of requiring scientists to get a second opinion from a neutral third party (an IRB) on research study designs involving human subjects. An central element of IRB review is to ensure that study subjects know what they’re getting into - meaning their consent to participation in the study is well-informed.

The Common Rule grew out of an earlier analysis called the Belmont Report, which was commissioned in direct response to the Tuskegee Study. The Report establishes a clear distinction between routine individual healthcare and scientific research. Unfortunately, the line is blurry because individual healthcare sometimes uses the tools of scientific research. Here’s how the Report describes the problem:

The distinction between research and [healthcare] practice is blurred partly because both often occur together (as in research designed to evaluate a therapy) and partly because notable departures from standard practice are often called “experimental” when the terms “experimental” and “research” are not carefully defined.

So far, so good. Where stuff hits the fan is with the Common Rule’s un-careful definition of the term “research.”

Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.

Lawmakers intended for their specialized legal definition of research to reinforce the Belmont Report’s exclusion of individual healthcare from human subjects review, but they evidently failed to appreciate the fact that individual healthcare is often at least somewhat systematic and it sometimes contributes to generalizable knowledge (e.g. the scientific publication of case reports). Lawmakers also failed to foresee that scientists and institutional administrators might intuitively drift back to the dictionary definition of research:

Studious inquiry or examination; especially: investigation or experimentation aimed at the discovery and interpretation of facts, revision of accepted theories or laws in the light of new facts, or practical application of such new or revised theories or laws.

If my doctor did not apply the dictionary definition of research to my individual healthcare I’d find a new doctor, pronto! A consequence of the Common Rule’s sloppy definition of the term research is that many modern institutions have fallen into the groupthink belief that the IRB’s purview includes any form of research that in any way involves human subjects. Employees screwing around with beer on the weekends? You betcha! That’s human subjects research, alright! Watch out, America’s Test Kitchen - the bioethics police may be coming for you next.

When the problem is seen through the individual healthcare lens, it becomes clear that the Common Rule never intended to interfere with self-care. The Common Rule was actually intended to prevent research institutions from interfering with individual medical treatment, including self-care. The groupthink failure to understand the sloppy legal definition of “research” has put us into a situation where ethics committees are making bids to replicate the medical withholding abuse of Tuskegee - instead of their actual charter to prevent it.

It’s important to note that self-care includes well-being. If it makes me happy to drink vaccine beer, prick my own finger, and test my own blood then ethics committees have no business demanding an IRB review to determine what I can or cannot do with my own body. The law allows institutional ethics committees to argue that a given experiment isn’t a scientifically useful way to spend institutional resources, but it’s unethical (and arguably illegal) for them to demand veto authority over individual healthcare activities.

An additional risk is that bioethics authoritarianism can needlessly inhibit scientific progress. That’s immoral too.

I believe it’s my civic duty to tell bioethicists to butt out of my self-care. Even if it means they try to fire me [1].

Song of the day:

[1] There’s a special place in my heart for Sister Sally Butler: “This is my church. If they don’t like it, they should leave. I’m not going to leave just because of the hierarchy,” Butler says. “But if I stay, I have to try to clean house.”

Appendix A: Self-experimentation does not meet the specialized legal definition of human subjects research

A federal law known as the Common Rule requires that research involving human subjects be pre-approved by an Institutional Review Board (IRB). Although a plain language analysis might intuitively suggest that the current study is a research project that involves a human, it is important to be aware that the Common Rule uses highly specialized definitions of the terms “human subjects” and “research.” In this Appendix, I argue that self-experimentation does not meet these definitions.

The Common Rule was established as a response to instances in which investigators abused research subjects by performing procedures without consent (such as in the Nazi atrocities) or by withholding information and treatments (such as in the Tuskegee Study). Common Rule section 45 C.F.R. § 46.102(e)(1) defines the term “human subject” based on a relationship between a living individual and an investigator conducting research.

(1) Human subject means a living individual about whom an investigator (whether professional or student) conducting research:

(i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or

(ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

When one individual investigates his own body, there is no potential for an abusive investigator-subject relationship. There is a legal rule known as the absurdity doctrine, which states that a statute is not being interpreted correctly if the interpretation defies common sense. Since it is impossible for a self-experimentor to fail to obtain his own consent, the idea that the Common Rule regulates self-experimentation fails the absurdity doctrine. A single investigator cannot be his own subject any more than he could marry himself or sign as both promisor and promisee in a legal contract.

We can gain further insight into legislative intent by considering the Belmont Report (NCPHSB, 1979), which served as the ethical foundation for the Common Rule. A key principle enunciated in the Report is Respect for Persons:

To respect autonomy is to give weight to autonomous persons’ considered opinions and choices while refraining from obstructing their actions unless they are clearly detrimental to others. To show lack of respect for an autonomous agent is to repudiate that person’s considered judgments, to deny an individual the freedom to act on those considered judgments, or to withhold information necessary to make a considered judgment, when there are no compelling reasons to do so.

IRB disapproval of self-experiments would be a violation of this principle, because it would obstruct the self-experimentor’s actions even though those actions are not clearly detrimental to others. The fact that regulation of self-experiments violates core ethical principles the Common Rule is based on provides further evidence that self-experimentors do not meet the legal definition of human subjects.

Even if one were to accept the proposition that investigators can serve as their own subjects, self-experimentation in pursuit of individual healthcare would still fail to meet the legal definition of the term “research.” The Belmont Report describes individual healthcare practices as:

designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success.

The distinction between healthcare and research is based on whether the treatment (or lack of treatment) is based solely on what is best for a particular individual’s health. If a self-experimentor would have given themselves the treatment for their own health or well-being anyway, then the activity qualifies as healthcare practice, not research. It’s important to note that a self-experimenter is better positioned to judge what serves his own health and well-being than any third party.

The Belmont Report explicitly acknowledges that experimental procedures can be an integral part of personal healthcare:

When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research.

The Report, and the Common Rule law that sprang from it, do not demand institutional review of individual healthcare activities, even in cases where a healthcare practitioner makes use of the scientific method. This makes sense, from the standpoint that institutionalized interference with personal healthcare activities is one of the problems the Common Rule was designed to solve.

The purpose of this study is to investigate the effect of a food-grade bioengineered BKV yeast product on my own well-being and to investigate the effect of the food on the structure and function of my immune system. Although the study does not investigate disease, it is conceivable that immune-mediated suppression of non-pathological BKV infection could have general health effects, such as improved feelings of well-being or maintenance of the healthy structure and function of my urinary tract (the primary site of common asymptomatic BKV infection). I also hope that eating BKV VP1 yeast might support general innate immune responses that could promote my well-being (Zhang et al., 2026). Pursuit of these possible immune system structure-function benefits serves my individual health interests.

When designing the study protocol, I anticipated that the experiments might be publishable. I do not view this as a valid standard for triggering IRB review, because neither the Belmont Report nor the Common Rule mention publication as a defining factor in the distinction between healthcare practice and research. Publication cannot serve as a bright line standard because physicians often publish case reports about individuals they’ve treated as part of normal healthcare practice without IRB review.

In summary, self-experiments designed to support my own well-being fail to meet the legal definition of human subjects research on multiple counts. This supports the common sense view that I am not required to request IRB permission to pursue my personal healthcare goals using my own resources in my free time.

I have a flashbulb memory of seeing the initial bar graph on Amin’s computer screen. The mice Safoura fed with vaccine yeast were mounting a response! Vaccines can be food! This changes everything! I remember feeling a little dizzy from the eureka moment.

Tina Saey’s elegant reporting in Science News shows that perception of the eureka is still eluding some of my colleagues. I have no hard feelings about the controversy - it’s a respectable difference of scientific opinion on the quaking landscape of a surprising paradigm shift. I’ve been doing vaccine research for 30 years, and I myself couldn’t see the promised land until very recently1.

The basic problem for vaccine scientists has been our collective failure to understand the anti-vaxxer viewpoint. Our response for the past half century has been to imagine that we can rebuild public trust in vaccines with displays of increasingly stringent FDA approval standards. This approach backfired. Imagine if I set out to do safety testing on a banana, and I dressed up in a hazmat suit and handled the banana with tongs. You wouldn’t think, “Wow, Chris sure is thorough with this banana safety testing” - you’d think “Wow, it looks like bananas might be about as safe as nuclear waste.” All the elaborate security theater we’ve been doing ended up putting anti-vaxxers in charge of the FDA. High five, vaccine community!

Of course, the FDA drug approval track isn’t just about safety - the main purpose of the approval system is to document that the drug works for its intended medical purpose. I can’t sell you a banana with the unapproved label claim that it will prevent strokes and reduce the risk of kidney stones. It’s plausible that the potassium in a banana might have salutary health effects, but I can’t make a conclusive claim about it unless it has FDA drug approval. On the other hand, I can still sell you the banana as a consumer product that meets federal food safety standards. It’s only illegal to tell you the banana is a safe and effective drug.

I know and love some deeply committed anti-vaxxers, and my openminded debates with them have helped me see that distrust of Big Pharma is at the center of their concerns. That’s fine! I don’t trust Big Pharma either! I would feel much better if Big Pharma’s medical claims were being evaluated by a neutral third party - as opposed to the system we have now, where Big Pharma self-tests its own products under the expensive and time-consuming security theater micromanagement of a potentially corruptible government agency. I also object to the fact that the reward on the other side of the regulatory wall is a de facto product monopoly. This is not what capitalism looks like. A capitalist system would use product reviews and third-party testing, like we have for practically all other categories of consumer goods.

This is why the fact that vaccines can be food is so earthshaking. We suddenly have a new path where we can lawfully put away the hazmat suit and just eat the damn banana. And Consumer Reports, Consumer Lab, and America’s Test Kitchen can help us figure out the best bananas.

One issue my brother and I wrestled with while we were developing vaccine yeast was whether the word “vaccine” is a self-contained claim of medical efficacy. In this regard, the anti-vaxxers have been doing us a weird upside-down favor with their claims that some vaccines are ineffective. Another way of thinking about it is to imagine setting up a Phase 1 safety trial under FDA guidance. I would be required to tell trial volunteers that the goal is to investigate the safety and possible efficacy of a new vaccine product. I wouldn’t be allowed to tell the volunteers they’re drinking Happy Funtimes Green Yeast and decline to mention the possible vaccine effects. In short, the word vaccine by itself isn’t an efficacy claim - it’s an expression of a possible health effect the food might plausibly have. Sometimes a banana is just a banana.

Song of the day:

I got my annual flu and covid vaccines a few months back. I’m 55, so the pharmacist insisted that I lie to him about having a “risk factor” before he could administer me the routine covid shot. I wanted to tell him the honest truth: my risk factor is that I have a really bad case of the RFKJ-is-incompetent brainworm that’s going around. But that probably wouldn’t have gotten me the life-saving medicine President Trump and I both know we need.

But let’s not dwell on political grievances! This post is about a brighter future. This week, our group posted breakthrough findings showing that ordinary brewer’s yeast can easily be turned into food-grade vaccines. And by “easily” I mean I literally conducted the entire experiment on an ordinary household budget in my own home kitchen. Vaccines can be delivered in the form of food! It means the new category of vaccines can be regulated as food - and people can choose for themselves whether to try them. Some additional detail on the discovery is here.

I’ve spent the past 15+ years working to develop a traditional injection vaccine targeting a group of viruses you’ve probably never heard of, called polyomaviruses1. They cause serious problems, including an incredibly painful bladder condition that often affects people who get bone marrow transplants. On a visit to a pediatric transplant hospital about a decade ago, my host told me they had to install soundproofing in the wards, because sometimes the bladder pain makes the kids scream so loud at night it wakes everybody up. I gracefully assimilated the upsetting knowledge. Then when I got back to my hotel room I put my face in my hands and broke into heaving sobs. If the mental image of children wailing in agony isn’t bad enough, I also felt acutely overwhelmed by the fact that I know how to solve this goddamn problem - but there’s a glacial wall of license-wrangling, technical development, and impenetrable regulatory bureaucracy between me and the desperate families literally screaming for my help. They were tears of frustration.

Posting the edible vaccine papers gives me tears of relief. I know how to breach the glacial wall.

I’m a long-time Asimov fan, so I of course watched the AppleTV adaptation of Foundation. The thought that has begun creeping into my imagination is that these food-based vaccine approaches are so simple the information can theoretically survive a civilizational collapse. People living in caves could just about practice this art! The simple knowledge that beer can be a vaccine could shorten a dark age. Meantime, fewer children screaming in agony would also be pretty nice.

Scientific preprints (Zenodo)

“An Edible Polyomavirus Vaccine” Soleymani, Tavassoli, et al.

“Vaccine Beer: A Personal Healthcare Report” Buck, CB.

Media coverage

•My hat is off to Science News’ brilliant Tina Saey. Her balanced coverage of the controversies in this strange new market space is truly excellent.

•I wouldn’t have believed that this story could be told in seven minutes, but the friendly team at the Canadian Broadcasting Corporation’s evening show As It Happens did so very deftly (vaccine beer story starts at minute 16:25)

•Hats off to The Times of London’s Will Pavia - it takes great skill to weave a little playfulness into his high-accuracy coverage of this complicated science.

•Succinct (and entertaining) coverage from Futurism. Couple other stories here.

•The vaccine science we’ve been developing is an uplifting story of international cooperation, with co-authors hailing from Iran, Lithuania, Ghana, and Mexico. My ancestry is half English and half German. Beer is in my blood?

•’s blog, More is Different, is a model example for the idea that all scientists should maintain a science blog. Long live peer-to-peer review!

•Ronald Bailey’s coverage in Reason Magazine insightfully highlights my view that competitive free markets can be a powerful force for human liberation.

•Some coverage of current controversy.

•This Progress, Potential, and Possibilities appearance was a fun conversation.

•On February 4, I was placed on “non-adverse” paid administrative leave. As of May 5, I have received no communications from my employer about when the leave might end. Sort of akin to these stories. Fortunately for me, my kitchen is now a tricked-out molecular biology lab. I’m treating it like a sabbatical.

•Articles from The Independent and Zymurgy.

Song of the day:

You will now be able to stay home, brother

And make beer during commercials, because

The revolution will put you in the driver’s seat

The revolution will be live

-Mashup of Gil Scott-Heron’s 1971 masterpiece, “The Revolution Will Not Be Televised”

Humankind has gotten really good at sequencing minuscule amounts of DNA, even from hard-to-extract samples like ancient bones. The sequencing process is exquisitely tailored to DNA, such that there’s essentially zero chance the sequencing would work for alien life that uses subtly different genetic material. On the other hand, a current hypothesis for our solar system (and perhaps the Milky Way as a whole) is referred to as “panspermia” — the idea that living microbes are sometimes transmitted between different worlds via meteorites. The panspermia hypothesis predicts that DNA sequencing methods designed for life on Earth should work just fine for life found elsewhere.

In two jaw-dropping papers this week, scientists describe the discovery of key building blocks of life on Earth, including the four bases of DNA, in samples returned from an asteroid called Bennu1. Niether the papers nor any media coverage I’ve seen mentions any attempt to extract or sequence DNA that could hypothetically be hidden in the sample. This makes me want to put my forehead on my desk. Contamination of the samples with Earth-based DNA is of course a concern for the proposed experiment, but any sequences from Bennu would definitionally have to be highly distinct from any sequences we’ve ever observed on Earth. Sequencing is the first experiment I would have done after opening the return sample.

It’s hard to imagine any attempts at sequencing were done comprehensively (using different sample extraction, amplification, and sequencing devices) and just not reported. Refusing to report negative data simply because you find the data disappointing is a known scientific no-no.

Eyes open, Team Bennu! At least give it a try!

There’s an old med school aphorism that goes:

When you hear hoofbeats, think horses, not zebras

It’s reasonable advice for a battlefield or an emergency room — where snap-diagnosis is crucial — but in other areas it can be a truly terrible heuristic. For people who happen to have a rare disease (which is estimated to sum up to about 10% of the population) the aphorism should make them angry. I’ve served as a patient advocate for friends with rare diseases, and I’ve hardly ever been angrier in my whole life than the time I watched a physician tell my zebra friend he was a horse until proven otherwise. It landed in my mind basically as, “I can’t figure you out, so why don’t you just go home with this horse tranquilizer and die already.”

I’m a research scientist, not a physician, and in grad school I was basically taught that when you hear hoofbeats, your experiments had better be able to tell the difference between horses and zebras. I’m increasingly feeling a little angry about the “think horses” orgy the astrophysics establishment has been tying itself into pretzels with on Atlas. These so-called “dark comets”1 are truly strange — and the strangeness just makes me think pretty much the exact opposite of horses. It makes me wonder whether Atlas is actually even weirder than the black-and-white zebra stripes revealed in some of the latest telescope images. Maybe the aphorism should be:

When you see zebras, think zoobreak

When I initially heard reports of exceptionally strong solar flares this week, I thought “nah — can’t be Atlas — it’s way over on the other side of the Sun.” Then my AI taught me that the Sun rotates on its axis every 26 days. If Atlas induced sunspots on the other side of the sun 13 days ago then the flares would be pointed at us now.

A scientific hypothesis is only as good as its experimentally testable predictions. Cheap predictions are especially high-value. So the first thing I did was check the record for Oumuamua, and bingo — there were exceptionally strong solar flares around the time of its closest approach to the sun (known as perihelion). A newer dark comet called Virgis2 will reach perihelion this coming Sunday. The flare hypothesis predicts intense solar storms late next week3.

A brilliant study by Beatriz Villarroel used archival photographic plates from the 1940s and ’50s to look for lights that appeared only transiently in the night sky. Villarroel found more than 10,000 transient lights occurring in an era long prior to the launch of the first satellite. She inferred that the objects must have been reflecting sunlight down from high in outer space because there was a dearth of transient lights in the Earth’s shadow. The amazing surprise is that the lights were statistically more common around the time of nuclear test detonations. The hypothesis that dark comet perihelions correlate with solar flares could be tested the same way — the prediction is that after exceptionally strong historical solar flares we might find a single tail-less transient object fleeing the inner solar system in old telescope images.

And guess what, horse-lovers! I’m still not necessarily invoking aliens! If Atlas is secretly much more massive than we think then I can easily imagine its gravity roiling the Sun. Or I can invoke the idea that dark comets have some kind of dark matter that emits some kind of dark energy that isn’t adequately explained by current physics. Picture me derisively waving my hands and saying “woo woo” while offering you a naturalistic explanation that doesn’t make any experimentally testable predictions.

Of course, I’m also not not invoking aliens. If the solar flare hypothesis were to prove true then aliens would strike me as a way less zebraistic explanation than invisible pink dark matter unicorns4.

Songs of the day: Beacon gets my nod for brainiest science-inflected band out there. Keep your eyes peeled for zebras in the Harm video.

Although I wholeheartedly embrace the key arguments in Avi Loeb’s classic post “Extraordinary Evidence Requires Extraordinary Funding,” I reject the title claim. Sometimes it’s true, but sometimes it’s not. For example, my current work transmogrifying vaccines into beer is a good example of cheap-but-extraordinary evidence. The whole point of the project is how cheap it is.

The first step in obtaining extraordinary evidence is identifying an important question. The second step is to creatively imagine which available explanations can best account for the existing pool of evidence, and then develop strategies for experimentally testing the predictions of each of the competing hypotheses.

Deciding which hypotheses to test is the step where the funding issue carries the most weight. If the most enticing hypothesis on the table costs a billion dollars to test - but there are also some extraordinary explanations that could easily be ruled out in an afternoon - then a wise scientist might first scratch the cheap-to-test hypotheses off the list before going down on bended knee to beg for extraordinary funding.

Which brings us to Mars. Loeb has estimated that Atlas has a minimum mass of 30 billion tons, but it’s hard to know whether its mass could be significantly greater than that. An extraordinary (but technically plausible) hypothesis is that Atlas could be a cooled neutron star. Since neutron stars are often highly magnetic, it would comport with the hypothesis that some of Atlas’s anomalies could be accounted for by the presence of a strong magnetic field. A testable prediction is that when the hypothetical neutron star passed close to Mars, it would have bent Mars’s orbit. The needed experiment is dirt cheap - somebody with a telescope just needs to have a quick look to be sure Mars is still exactly where it’s supposed to be.

Neutron stars are typically a little more massive than the Sun. If a collapsing star were an order of magnitude smaller than the Sun, there wouldn’t be enough gravity to keep the neutrons compressed and the core would quickly decay into protons and electrons and go back to the density of ordinary matter. My layman’s sense is that it might be possible to hand-wave some kind of dark matter hocus-pocus that could hold a planet-mass object together in a compressed neutron-rich state. In a thought experiment where an object with the mass of the Earth had passed Mars at 30 million kilometers, my AI tells me Mars’s orbit would have shifted by a barely detectable amount. If Mars is still exactly where we think it should be then it will cheaply rule out the extraordinary hypothesis of planet-sized masses.

Song of the day:

Back in August, I speculated that the third interstellar object, Atlas, might have a strong magnetic field that could account for some of its strange behaviors. Since then, the list of anomalous behaviors has continued to grow, and it looks to me as though several of the newer anomalies can also be accounted for under the hypothesis that Atlas has a magnetic field and a thin atmosphere.

Auroras are produced when the Earth’s magnetic field funnels charged particles from the solar wind down to the north and south poles. When high-energy particles excite atmospheric gases like oxygen and nitrogen, it causes them to emit photons (the same basic principle as familiar neon lights). Different gases emit different colors when excited - oxygen shines green, while nitrogen predominantly emits blue light. In September, the light coming from Atlas shifted from predominantly red to predominantly green. In the past week, Atlas became much brighter and its color shifted from green to blue. Maybe these colors are being emitted by auroras, alongside the reflected sunlight? An analogy would be to picture a white barn illuminated by moonlight. If you flip on a big neon sign (an aurora) on the side of the barn then the barn will suddenly be much brighter, and its overall hue will be red-orange instead of white.

The hypothesis that Atlas has an oxygen-nitrogen atmosphere makes the experimentally testable prediction that these gasses will be visible in the far-ultraviolet (FUV) spectrum. NASA and other space agencies have so far refused to use existing FUV-equipped space telescopes to image Atlas. In addition to visible light, auroras emit X-rays - which space agencies have also neglected to look for. Just look up, NASA!

Another interesting anomaly from the past week is that Atlas has begun to decelerate very slightly and has moved very slightly outward, away from the sun. One explanation for the non-gravitational acceleration could be that Atlas is being pushed by the venting of large amounts of unseen gas (oxygen-nitrogen?). An alternative explanation could be that a strong magnetic field is functioning like a sail that’s pushing Atlas around in the solar wind. Both explanations will become less convincing if Atlas comes out from behind the sun this week on a corrected course aimed directly for Jupiter or some other interesting-to-aliens destination1.

An older anomaly is that there seems to be a lot of nickel around Atlas, but with little or no iron. Nickel and iron are produced by similar stellar process and they’re chemically similar enough that it’s rare to see the two elements separated from each other. Metallic meteorites are always an alloy of the two metals, with iron being predominant. The magnetic field/atmosphere idea, which I’ll call the Worlorn2 hypothesis, offers a possible solution for the nickel puzzle. In an oxygen-rich atmosphere, iron turns to rust much faster than nickel. Rust isn’t magnetic, so the idea is that all the iron on the surface of Atlas is rusted, while some of the nickel remains metallic. In that scenario, the hypothetical magnetic field could keep nickel filings aloft, in the same way a strong fridge magnet can organize iron filings along magnetic field lines. As I proposed back in August, the idea of magnetically levitated dust could explain Atlas’s anomalous sunward “anti-tail.”

If you’re keeping score, it seems like the Worlorn hypothesis could account for anomalies 2, 3, 4, 8, 9, and 10. Pretty good, for a hypothesis that isn’t invoking aliens! Although I gotta say the Worlorn hypothesis doesn’t really move the needle on my alien-betting calculus. I’ve been moving small percentages of my investment portfolio into gold, on the guess that there may soon be enough anomalies to spook the markets. It’s not investment advice — just an affirmation that my money’s where my mouth is on the bet that aliens might have installed a magnetic field, for the sensible purpose of deflecting cosmic rays. Or who knows. Maybe it’s actually intended as a neon sign.

Song of the day:

In Rendezvous with Rama, Arthur C. Clarke imagines a mission to intercept an enormous alien vessel that’s passing through the solar system. When the interstellar visitor is first spotted, its preliminary scientific designation is 31/439. In Clarke’s imagined future, astronomers have exhausted all the names from Greek and Roman mythology, so they turn to the Hindu pantheon and settle on the common name “Rama.” In present-day reality, a large interstellar object, initially designated A11pl3Z C/2025 N1 3I/ATLAS, is passing through the solar system. This fascinating visitor hasn’t been assigned a plain-language common name.

As strange as it may sound, the origin story for my virology blog is entwined with the first known interstellar object, Oumuamua. I’m a pretty good fit for the newly described “otrovert” personality type - which means I’m reflexively attracted to evidence that challenges dogma. When Harvard astrophysicist Avi Loeb started his blog - which initially covered Oumuamua and now covers all sorts of unorthodox hypotheses for how we can search for evidence of extraterrestrial life - I instantly found it amazingly shiny.

I’ve gradually arrived at the opinion that all scientists must have blogs. First of all, it’s fun to write about science - and writing things down in a form I hope will be persuasive helps me organize my own thinking. More importantly, the DOGE fiasco overwhelmingly reinforces a time-honored concept: it’s important for scientists to share our observations in ways the general public can grasp and start playing with themselves. Blogging also gives me opportunities to hear where there may be holes in my logic - which helps me triage and discard bad hypotheses before they waste too much of my time. Win win win!

Emerging observations of 3I/ATLAS are unorthodox. It’s traveling in the same plane as the planets and it will do flybys of Mars, Venus, and Jupiter - the three other places in the solar system where humans suspect there might be life. The object has some kind of dusty cloud suspended over its sunward face, but there’s no discernible cometary tail. This is very strange. The second interstellar object, 2I/Borisov, was clearly comet-like and it showed a visible tail at the distance from the sun that 3I/ATLAS is currently at. In Avi Loeb’s comments sections, I’ve been generating some layman’s hypotheses for how a dusty cloud could defy gravity without forming a tail - and some of the hypotheses (such as the one imagined in the cover art) predict 3I/ATLAS might emit X-rays. Astrophysicists! Please use Chandra!

The size of 3I/ATLAS remains uncertain, but it could be as large as 10 km - about the size of the object that wiped out the dinosaurs. It’s extremely unlikely for interstellar objects of this size to show up during the decade or so where we’ve been carefully searching for them. There basically isn’t enough ordinary matter in the galaxy to easily account for it. ThreeI/ATLAS is delightfully weird!

My adherence to the scientific convention that one shouldn’t use arabic numerals at the beginning of a sentence highlights the awkwardness of the scientific designation for the third interstellar object. Every time I hold down the shift key to type the International Astronomical Union-authorized scientific name, it gives me a little twinge of covfefe. The most intriguing object in the sky needs a pronounceable common name that doesn’t remind me of rage-tweets.

I’ve spent a lot of time wrestling with virus names over the past few years. We’re constantly discovering new virus species, which has given our field a good workout for developing coherent naming conventions. In biology, familiar species have both a precise scientific name (for example, Rosa x odorata) and a common name (tea rose). The precision of approved scientific names is essential for scientific publications, but a love note about the dozen red Rosae x odoratae you got on Valentine’s Day would not smell as sweet. This where we currently are with 3I/ATLAS - we have an officially sanctioned scientific designation that simply doesn’t work very well as a common name. I’m beginning to see scientists play with common names like “3I” in blog posts, but I like this even less because in some fonts you can’t tell whether it’s 3I, 3l, 3|, or 31.

While it would of course be amazing to be the guy who coined the common name for the most interesting thing in the sky (sorry, God), I promise I won’t try too hard to make fetch happen.

If you don’t like any of my offerings, then I’ll happily get behind your efforts to make some other fetch happen. Just please. Not Old Three Eyes. And not Dusty McDustface. That’s the kind of fetch we’re gonna get if astrophysicists keep trying to make names like ThreeCapitalEyeSlashCapitalAyeCapitalTeeCapitalEllCapitalAyeCapitalEss1 happen.

• “Thria.” In virology, we often use portmanteaus (new words assembled from syllables or letters of existing words). For example, one group of viruses I helped name are called “adomaviruses” — a portmanteau that refers to the group’s split allegiances to ADenoviruses and polyOMAviruses. Another group of viruses I study uses names from Tolkien mythology. In the case at hand, I propose the name “Thria” — referring to THReeI/Atlas. I chose this particular combination of letters because it’s easy to remember and it also happens to coincide with the name of a suburb of ancient Athens. The Athenian suburb was roughly the same size as 3I/ATLAS.

• “Alaea.” In Hawaiian, the word ‘oumuamua means “messenger from afar arriving first.” The interstellar object with the common name Oumuamua was discovered by the Pan-STARRS1 telescope at the Haleakala Observatory on Maui. There has been controversy over the construction of some of the telescopes in Hawaii, and the common name is a respectful way of communicating the idea that the Haleakala summit has become a sacred place for all the world’s people. One of the telescopes in the ATLAS array that discovered 3I/ATLAS is on Haleakala, so implementing the Hawaiian language convention seems appropriate. The light from 3I/ATLAS is disproportionately red in color. In Hawaiian mythology, humans were formed from ‘alaea — Hawaii’s iconic red soil. It’s also a memorable word because it starts with some of the AtLAs initials. I’ve been slightly preferring Thria over Alaea because I wonder whether people would butcher the pronunciation as “ah-LAY-ah,” instead of the intended “ah-lah-EH-ah.” But whatever. Every time I speak a Chinese loan word without the tonal inflections I’m basically butchering it. Cost of doing business. On top of that, I may be giving English-speakers too little credit — I don’t remember hearing anybody butchering the first interstellar object as “OW-mwa-mwa.” So I guess I’d now vote for Alaea over Thria.

• “Atlas.” Although this is the simplest solution for the case at hand, it has the Clarke problem—the common name is already in use for an object with scientific designation S/1980 S 28 (one of Saturn’s moons) and for a star in the Pleiades cluster. I suppose the Clarke problem isn’t such a big deal. The weirder 3I/ATLAS gets the less likely it is there will be any confusion about which Atlas we’re referring to. I’m still in the process of brainstorming, but I’m beginning to prefer “Atlas” over Thria or Alaea2.

• “Sagittarides.” Ancient Greek has a variety of suffixes indicating filial descent. For example, the name Atlantis could be translated as “daughter of Atlas.” It could offer a systematic naming convention where interstellar objects are named based on the constellation or familiar star behind their trajectory. Atlas is coming from the direction of the constellation Sagittarius - so it could be “Sagittarides3.”

• “Worlorn.” Depending on how the November-December data shakes out.

Whether you like any of my common names or not, a central assertion of this post is that the IAU has to develop fetchier naming conventions for interstellar objects. Ideally, a serviceable common name should be embedded in the official scientific designation (along the same lines as 1I/’Oumuamua).

The new Vera C. Rubin4 Observatory in Chile’s Atacama desert is expected to detect dozens of interstellar objects in coming years  - so the observatory-based naming convention won’t work  because  it’ll confusingly make the next objects 4I/VCRO, 5I/VCRO, 6I/VCRO, etc. Maybe the fourth interstellar object could be a portmanteau like Fourubin? Then Fivera? Sivro? Descendant of background constellation? Or maybe we can all look forward to mispronouncing the names of Andean gods.

Song of the day:

With permission from the Stanford Library and the Berg estate, I’m posting a searchable copy of Berg’s January 5, 1979 letter to Senator Harrison Schmitt. I did some minor editing to improve online readability - including embedding hyperlinks to my guesses for the documents referred to in the letter.

I’ll save my own thoughts on the intellectual content of the letter for a separate post. Meantime, the provocative article title can give you a sense of where I’ll be headed.

Dear Senator Schmitt,

Please forgive me for the delay in answering your letter of November 8 asking for my views on Senator Stevenson’s intention to introduce legislation next year to regulate recombinant DNA research. I left for nearly a month-long trip to Japan shortly after your letter arrived and the accumulated chores and obligations that greeted my return kept me from responding sooner.

Lest there be any doubt about my views, let me be quite direct: I am unalterably and unequivocally opposed to legislation, whether federal, state, or local, that regulates research using recombinant DNA techniques. Such drastic and far-reaching action (or overreaction) is, in my view, unnecessary and therefore unwarranted. But, more importantly, I am concerned that such legislation and the inevitable bureaucracy it would engender could cripple important lines of biological and medical research that have become reliant upon the recombinant DNA breakthrough. In attempting to guard against what were never more than conjectural and are now highly improbable and unrealistic fears, such legislation would require costly expenditures and procedures in a vain attempt to obtain the impossible: assurances of zero risk. For myself and for many others that price is too great, the cost-benefit ratio unacceptably high. As I see it, the nation would gain little from such legislation and the losses would be excessive. Instead of seeking new ways of regulating this field of science I believe we should be exploiting, as vigorously as we can, the tremendous opportunities afforded by the recombinant DNA methodology. In doing so we should also be alert and ready to respond to any surprises that signal danger. But certainly we should not be erecting political and administrative barriers or bureaucracies that serve no useful purpose. Unfortunately, Secretary Califano is determined to do otherwise (see attached Nature commentary and Federal Register December 22, 1978). As you well know, creativity, intuition, knowledge, and persevering effort are the hallmarks of first-rate science. The administrative edifice that has already been constructed to govern recombinant DNA research frustrates the first two and impedes the last. Having a cumbersome, inefficient, and unresponsive bureaucracy centered in Washington-Bethesda controlling the design and performance of experiments is incompatible with effective research.

Interminable meetings of local committees that have too little understanding of the experimental details, opportunities, or putative risks they must judge consume scandalous amounts of time. Before experiments can be initiated to determine the significance or usefulness of promising leads, breakthroughs, or hypotheses there are frequently months of review, discussion, and paper-pushing. If, in the progress of the research, some alteration in the protocol becomes necessary or advisable, further time-consuming consultations and deliberations are required. Is it any surprise that an increasing number of leading American scientists, having had enough of these burdensome restrictions and stultifying administrative demands and anticipating still worse times, are turning to foreign laboratories for relief? However one feels about the propriety of their decisions and actions, we cannot escape the signal and its implications: important science — research that society wants done and is paying for — will leave the US to be done in a more hospitable setting. But what are the prospects for those scientists who do not have this option? Morale and enthusiasm will very likely wane, the overall research effort will be eroded, and the momentum generated by the recombinant DNA breakthrough could dissipate. This may please the “less knowledge is better” and environmentalist forces, but for most it is a calamity we can ill afford.

The recombinant DNA controversy continues to puzzle me. Those of us who signed the 1974 “Moratorium” letter did so not because we were convinced of imminent danger or disaster (as it has often been misrepresented), but because we believed the issue needed to be raised and examined carefully and critically before, not after, proceeding full-speed ahead. But what began and should have remained principally a scientific issue was captured and exploited by sensationalist journalists (see attached Nature commentary for a recent example), by environmentalists, and single-issue public interest groups who fail to consider the wider consequences of their own narrowmindedness, and by demagogic scientists and politicians who prefer to manipulate rather than understand the issues. For me and many of my colleagues this exercise in science and public policy has become nightmarish and disastrous.

Rather than legislative or administrative actions to curb recombinant DNA research, we need to look seriously at whether the unlikely risks that remain warrant huge expenditures of money to support the present machinery that regulates recombinant DNA research. My own early concerns that some recombinant DNA experiments might carry risks have long been dissipated. The data, discussions, and experience of the last four years have convinced me that our earlier concerns are no longer warranted. I now believe that society has more to fear from the intrusions of government in the conduct of scientific research than from recombinant DNA research itself. Initially, I was full of hope and optimism that we could act wisely and decisively to develop procedures that would promote research using this promising new tool and minimize or eliminate whatever risks that pertained. But from any vantage point I see only a victory for the politicians of science, rather than scientists. I and most of my colleagues are growing increasingly apprehensive about the outcome of such victories. To counter individuals and organizations promoting “Science for the People” we need “People for Science.”

I greatly appreciate your invitation to state my views on this matter. I am sorry I could not do it sooner. I also wanted, particularly, to commend you on your letter to Science opposing oppressive legislation to control scientific research. It is reassuring to know that there are some in our government councils who share, through experience and understanding, our love for science. I often recall your statement that if you were reentering science today, biology would be your first choice. I’d be happy to fill you in and keep you abreast of developments in the recombinant DNA field, should you decide it’s really not too late. Perhaps you’d be interested in some of the scientific happenings in our lab – a recent New York Times article summarizes some of our current work that will soon appear in Nature.

Respectfully,

Paul Berg

1) I have a concept of a plan for bringing down the price of eggs. On Presidents Day, I worked from home to design a fusion of the receptor binding domain of influenza H5N1 genotype B3.13 hemagglutinin to a stabilized Helicobacter pylori ferritin scaffold1. The sequence of the synthetic nanoparticle was subjected to extensive optimization for expression in yeast, so part of my week was spent refreshing my knowledge of yeast molecular biology literature. The synthetic ORF - with or without ER signal - will be moved into 2µ expression plasmids I developed encoding synthetic GAL10 or MAL32 promoters. Induced yeast will be fed to chickens, in hopes of rendering them immune to bird flu.

2) A recent paper from a group in China teaches that oral administration of yeast expressing surface-displayed bird flu antigens can protect chickens against a lethal challenge. In parallel to the ferritin constructs, I also spent time this week building on Lei and colleagues’ findings by designing a full H5 ectodomain appended with a glycosylphosphatidylinositol anchor. It seems conceivable that multifold cells in the chicken small intestine will be able to use sialylated glycans to tear away lipid-anchored HA trimers and transcytose the antigen for presentation on follicular dendritic cells in underlying lymphoid structures. This could be an improvement over the covalent Aga2p display used in Lei et al. I’m currently in the process of surveying the scientific literature to achieve a better understanding of other design parameters. For example, this past week I scheduled teleconferences and physical workplace discussions with colleagues who helped me brainstorm a concept of a plan in which the symmetry mismatch between hemagglutinin and neuraminidase could be used to zipper together a kinked 12 x 12 array using a scaffoldless Spytag approach. Another emerging idea we’re playing with is to use the hemagglutinin-neuraminidase tetramer of Newcastle disease virus (against which chickens are routinely vaccinated) as a symmetry-mismatched recall antigen that could help rapidly elicit de novo responses against HA trimers.

3) In a separate line of work this week, I’ve begun an effort to learn the complicated search syntax for Google BigQuery so I can extract metadata from NCBI SRA cloud records. This is the final step before uploading 20 TB of data representing 750,000 SRA records into a federal cloud repository. The upload will enable scientists around the world to quickly search for viral sequences in various datasets, including de-identified human cancer datasets. The exceptionally skilled bioinformatic scientist who had been spearheading the upload is unavailable because he’s embroiled in emergency damage control after losing a member of his small and highly interconnected team in the Valentine’s Day Massacre. I’m worried more staff members (such as myself) will be randomly fired and I won’t be able to complete the upload. It took several years and many millions of CPU hours to compress the library into a laptop-searchable form. This incompetent HR clown show you guys have been putting on is threatening to flush the whole thing down the toilet. This is not what efficiency looks like.

4) I enjoyed two workdays in which I distracted myself from the incompetent clown posse with the engrossing task of using HHpred and AlphaFold to deep-annotate Pox mesodorylaimus185453, the first known poxvirus of nematodes. The most interesting observation is a homolog for interleukin-6. This comparative virology discovery provides basic science information about the hidden mechanisms viruses have been using to manipulate immune responses for hundreds of millions of years. At a translational level, nematode poxviruses might one day be useful for treating parasitic worm infections.

5) A colleague down the hall pretty much singlehandedly developed a cure for a rare form of cancer called ocular melanoma. She’s among the strongest, most disciplined scientists I’ve ever worked with. My unbreakable colleague was fired in the Valentine’s Day Massacre. To reduce the mounting risk of experiencing workplace anger management issues, I used work hours to re-read MLK’s “Loving Your Enemies” sermon.

There’s another reason why you should love your enemies, and that is because hate distorts the personality of the hater. We usually think of what hate does for the individual hated or the individuals hated or the groups hated. But it is even more tragic, it is even more ruinous and injurious to the individual who hates. You just begin hating somebody, and you will begin to do irrational things. You can’t see straight when you hate. You can’t walk straight when you hate. You can’t stand upright. Your vision is distorted. There is nothing more tragic than to see an individual whose heart is filled with hate.

I also refreshed my memory of the complementary self-help advice in FDR’s 1936 Madison Square Garden speech.

We had to struggle with the old enemies of peace—business and financial monopoly, speculation, reckless banking, class antagonism, sectionalism, war profiteering. They had begun to consider the government of the United States as a mere appendage to their own affairs. We know now that government by organized money is just as dangerous as government by organized mob.

Never before in all our history have these forces been so united against one candidate as they stand today. They are unanimous in their hate for me—and I welcome their hatred.

I should like to have it said of my first Administration that in it the forces of selfishness and of lust for power met their match. I should like to have it said of my second Administration that in it these forces met their master.

Spending the workday writing this email helped me renew my long-term professional commitment to serving as a happy scientific warrior in the eternal struggle against organized money2.

The Lost Lesson of Tuskegee

CHRIS THARRINGTON

DEC 19, 2024

In the Spring of 2021, I received my first two doses of Covid mRNA vaccine at a mass vaccination clinic set up in a county rec center. Remembering that my brother had a recent history with bad respiratory infections, I urged him to get vaccinated. He said he was worried about the vaccine “because Tuskegee.” At the time, I was listening to the brilliant podcast Way Down in the Hole, in which hosts Jemele Hill and Van Lathan Jr. discuss each episode of The Wire. My brother’s thinking (or lack thereof) brought to mind an episode in which Jemele, in response to Van’s mystifying dislike of Popeyes spicy recipe said, “I so want to call you the N word right now.”

I suppressed my “N word please” reaction, took a deep breath, slowly exhaled, then respectfully asked “what do you mean when you say ‘Tuskegee’?” It turns out my brother, like most Black people, entertained the false belief that the organizers of the Tuskegee Study of Untreated Syphilis in the Negro Male (TSUS) secretly injected study subjects with syphilis - and he was concerned that the new Covid vaccines might likewise contain an infectious agent that would intentionally target Black men. My brother is an intelligent man whom I love very dearly. But seriously. I had to suppress an urge to shake him by the shoulders. I’m pleased to say that the calm conversational tone I managed to muster worked well for convincing my brother to reconsider and go get the shot.

My brother’s outrageous misapprehensions led me to something of a deep-dive into TSUS history. The opening sentence of a recently constructed TSUS memorial outside the National Library of Medicine succinctly summarizes the actual history:

The study, which was conducted without informed consent and withheld treatment...1

Unfortunately, my deep-dive taught me that the plaque’s emphasis is wrong. Entirebooks have been written about the fact that TSUS volunteers didn’t understand what they were signing up for, but an African American physician named Robert White has written a series of scholarly articles about the issue, and his arguments persuade me that the question is very complex, and it has been clouded by implicit class bias. When I project myself into the shoes of TSUS volunteers, the first thing I’m aware of is the fact that the Jim Crow South denied them access to education. When thinking about Tuskegee, I have to cognitively correct for my embarrassing upper-class, well read, subconscious gut instinct to think uneducated people are stupid. TSUS volunteers were intelligent autonomous adults. It’s a repulsive bigoted mistake to infantilize them as helpless victims. It’s also a gross oversimplification that gets in the way of learning the full range of lessons the TSUS disaster should have taught us.

The actual headline of TSUS is tidily encapsulated in the single word “withheld.” The lack of informed consent was only important because it was one of the methods TSUS organizers used to abusively withhold treatment. Withholding treatment was the fundamental ethical breach. The most horrifying aspect of the disaster wasn’t the fact that the volunteers in TSUS weren’t made aware of the medicines that could cure them of syphilis; rather, it was the fact that when some of the men independently learned about penicillin, the study organizers refused to give it to them, and told them not to seek it out at other facilities. White’s research has uncovered evidence that quite a few of the men refused to be victimized, and these men successfully received penicillin at a rapid treatment facility in nearby Birmingham. Again, it is a mistake to infantilize these men - they were individual human beings. Some of them recognized the abusive medical withholding for what it was and heroically defended themselves against it. When my brother initially refused the Covid vaccine, he was effectively doing the opposite. Without the calm and respectful advice of a loving brother he would have self-enrolled in his own private Tuskegee Study.

How did we slip into this bizarro opposite universe where the central lesson of TSUS has been turned completely upside down in many people’s minds? One part of the problem is illustrated by President Clinton’s choice to play with identity politics instead of explicitly enunciating the medical withholding problem in his 1997 speech apologizing for TSUS. Clinton said:

To our African American citizens, I am sorry that your federal government orchestrated a study so clearly racist. That can never be allowed to happen again. It is against everything our country stands for and what we must stand against what it was....The legacy of the study at Tuskegee reaches far and deep, in ways that hurt our progress and divide our nation. We cannot be one America when a whole segment of our nation has no trust in America...We need to do more to ensure that medical research practices are sound and ethical, and that researchers work more closely with communities.

The road to Hell is paved with good intentions. Clinton’s intentions in the 1997 speech were fine, but his focus on racism, combined with an emphasis on the need for medical ethics training programs for physicians and scientists, inadvertently suggested that many modern medical researchers might be some kind of latter-day Josef Mengles. This isn’t an effective way to instill trust in medical research. Small wonder that conspiracy theories swirling around new medicines like Covid mRNA vaccines persist to this day.

Apologizing for the fact that the government lied to TSUS volunteers is good, as far as it goes - but the main thing the government should also apologize for is its failure to develop policies that would have enabled rural Alabamians to afford the lifesaving medicines they so desperately needed. Withholding medicine through economic deprivation was the central problem of TSUS. But it’s politically easier to call out racist researchers than it is to call out lackadaisical legislators.

So what does all this mean for the present day? It means modern clinical trials have a lot of trouble recruiting African Americans. And it means the clinical trials I’ve volunteered for usually take many years to clear regulatory authorities and the experience comes with huge amounts of ritualized security theater paperwork, because all clinical trials are assumed to be ripe for abuse until pre-proven innocent. My brother illustrates the fact that the elaborate security theater around clinical trials doesn’t always improve trust in the medical system - it sometimes sows doubt.

Later in 2021, the lost lesson of Tuskegee meant that when an over the counter LabCorp test showed my antibody responses against the initial two doses of the Covid mRNA vaccine were shockingly close to zero, I had trouble getting a just-in-case J&J booster dose. In my first visit to a pharmacy, I had my sleeve rolled up, the syringe was on the table, and when the technician asked, “have you received a Covid vaccination”, and I told the truth. The technician put on a faux-regretful face and told me that I couldn’t have the booster dose. I didn’t put up much of a fight because I didn’t think it would do any good to play the role of the angry Black man. But I was angry. Medicine was abusively withheld from me. I channeled the Laurence Fishburne character in Miss Evers’ Boys and scheduled a successful J&J boost at a different pharmacy later in the week. It might be nice to hear an official apology for the fact that I had to lie to a healthcare provider to get a lifesaving medical treatment.

Finally, the lost lesson of Tuskegee is tragically illustrated by the words “delay” and “deny,” which were engraved on the shell casings found at the murder scene of UnitedHealthcare CEO Brian Thompson. The killer was referring to the ongoing insurance industry practice of abusively withholding medical treatments. When healthcare companies robo-deny payments for life and death medicines like insulin, the industry is replicating the central abuse of TSUS on a far larger scale. The fact that these new disasters are suffused with less racism than before can hardly be considered progress. We have to learn the top-level lesson that withholding medical treatment is wrong and then resolve to stop doing it.

I bet Covid wishes it could have given me serious brain damage. As I’ve outlined in the last few posts, seeing the strange and interesting dynamics of Covid infection firsthand has been sparking my creative imagination about how to kill the little bastards. One strategic victory a personified Covid might have thought it scored was when its multiple rebounds prevented me from flying to Italy for the annual Small DNA Tumor Virus Meeting - where I was slated to give a talk about a new vaccine approach being developed by two brilliant postdocs in our group, Safoura Soleymani and Amin Tavassoli. I’m increasingly imagining the new vaccine approach could be retooled for next-generation Covid vaccines. But the joke’s on Covid. My scientific partner Diana Pastrana delivered the talk in my place and colleagues report she knocked it out of the park. Sorry, Covid. We are still coming for you1.

The basic idea behind Amin and Safoura’s work is that if you don’t have to inject a vaccine using a needle then the usual time-consuming industrial-scale purification processes that require expensive equipment suddenly become unnecessary. If we could kick the expensive habit of using needles, we could theoretically have cheap food-grade vaccines. In a sense, the idea is simply harking back to older vaccines - such as early smallpox vaccines that were delivered intranasally or scratched into the skin - or oral polio vaccines that were sometimes delivered on a tasty sugar cube.

In grad school, I was taught that needle-free approaches only work because they use a live virus that’s capable of replicating and spreading to other tissues. That dogma has since been disproven by modern cholera vaccines, which consist of drinking some fluid that contains a harmless subunit of the cholera’s major toxin. Food-grade vaccines don’t have to be replication-competent.

Although we’ve been working to develop a traditional injection vaccine against polyomaviruses (disclosure: I receive commercial licensing royalties for that vaccine project), I still have residual intellectual trauma from the fact that it took us several years to convince investors to commit millions of dollars to producing purified polyomavirus-like particles in an expensive state of the art facility. And by “us” I actually mean Diana. She and I are both skilled in the art of talking to fellow scientists, but our licensing efforts revealed that I’m remarkably bad at convincing any investors to do anything - whereas Diana has some type of superpower. Diverse teams are stronger teams, as the saying goes.

In her talk at the Tumor Virus Meeting, Diana presented Safoura and Amin’s exciting emerging data showing that purified replication-incompetent polyomavirus-like particles (VLPs) give good vaccine responses when delivered intranasally or when applied to the skin with a cosmetic derma-roller. We’ve also been finding that brewer’s yeast engineered to express VLPs give pretty good immune responses when delivered intranasally or intradermally.

NASA has the famous motto “faster better cheaper.” Immune responses against the new food-grade vaccines aren’t necessarily “better” than traditional injection vaccines, but they’re definitely opening the door to an approach we’re calling “faster easier cheaper.” We can probably also add “safer” to our motto. Not to mention, “people like it more than getting jabbed with a needle.”

We initially chose brewer’s yeast simply because it was easy. Emilija Vasilliūnaitė - a Fulbright Fellow from Lithuania - was familiar with the robust yeast-based VLP expression systems her mentor, Alma Gedvilaitė, has developed. International collaborations are important! In parallel, we’re developing bacteriophages that can express polyomavirus VLPs in the types of bacteria that are used to ferment yogurt.

The new thinking my Covid infection inspired has suddenly expanded my view of which microbes we might want to use for food-grade vaccine approaches. The ideal vehicle would be something people routinely use as a food or probiotic and - importantly - the vehicle should be known to induce an effective Th1 response without the type of ineffectual IL-6/histamine/mast cell/allergic/worm-fighting/Th2 responses I hypothesize are flummoxing the immune system during Covid infections (see: “Bullfighting Covid”). Two examples of the ideal vehicle might be the Th1-skewed probiotics Saccharomyces boulardii and Latilactobacillus sakei. If anybody has any favorite organisms to suggest, we’re all ears2.

It’s conceivable the food vaccine approach could be used to quickly test the hypotheses presented in “Latency, Long Covid, and the Dreaded Rererebound.” The basic idea would be to load SARS-CoV-2 early proteins, such as defanged NSP3, into a VLP by fusing it to a minor capsid protein. The NSP3-bearing VLP could then be expressed in yeast or bacteria and we could see whether nasal or dermal exposure to the food-grade VLP preparation reduces the odds of having the type of Covid rebounds my husband and I just unhappily experienced. To the extent that latent infections are a primary driver of long Covid, it could also be interesting to see whether a food-grade NSP3 vaccine might make long Covid sufferers feel better by eradicating latently infected cells.

Our current team is small - consisting of Diana, Amin, Safoura, and a fifth team member, Claive Asiedu, who has been helping Safoura and Amin wrangle VLP production in yeast. I would love to see a thousand times more people independently working on food-grade vaccines. The most powerful aspect of the idea is that you don’t have to convince investors to give you millions of dollars for fancy equipment. The approach is simple enough that it could conceivably be within reach of a Science House kitchen. Are your ears burning yet, ?

Covid. Must. Die.

My current Covid experience reshaped my strategies for what I’ll do next time I get infected with Covid or other upper respiratory tract pathogens1. Under ordinary day-to-day conditions between infections I’ll plan to:

1. Get a booster dose of Covid mRNA vaccine every 4-6 months. I’m planning to take a daily Claritin for one week after the booster dose (see “Vaccines” section below for a rationale) 

2. Drink mint tea plus put plenty of mint family herbs in food

3. Pop an occasional quercetin or curcumin (or combo Nasafytol) alongside a regular multivitamin

4. Lucira test (combined nose and throat) a few days after known exposure or if I sense sinus soreness, throat soreness, sneezing, or coughing. Also asymptomatic group Lucira testing at family gatherings

After testing Covid positive, I’ll spend three weeks on the regimen below (in addition to the day-to-day regimen above). During my current infection, I stopped taking medications when my rapid antigen test (RAT) band faded. With hindsight, I can see it was a foolish sin against the 15th Commandment. In the future, I’ll stay on these meds for three continuous weeks regardless of what the RAT is doing.

1. 500 mg metformin twice a day (with food)

2. 20 mg famotidine (aka Pepcid, Zantac) twice a day

3. One spray in each nostril Astepro (over-the-counter generic azelastine) twice a day

4. 6 mg melatonin before bed

5. RAT every couple days2

6. During the first week after testing positive, get a booster dose of mRNA vaccine

7. No alcohol. Sigh.

•Antihistamines (azelastine, curcumin, famotidine, melatonin, quercetin). See: “Bullfighting Covid”

•Metformin: A front-line choice for defending myself against Covid is a drug called metformin. Metformin is among the safest, most efficacious, and cost-effective medicines for long-term management of diabetes. It has also been considered as a candidate anti-aging treatment. Sixty years of experience with daily metformin use shows that its only common side effect is nausea and diarrhea and this is usually a transient effect that fades with longer term use and can be mitigated by taking metformin with food.

Despite the fact that metformin is as safe as houses, it remains prescription-only. Fortunately, I have an excellent primary care physician who thanked me for sharing a series of overwhelmingly convincing randomized controlled clinical trials (RCTs) documenting metformin’s ability to reduce SARS-CoV-2 viral load, hasten the resolution of Covid symptoms, and prevent long Covid. He agreed to write me an advance “off-label” metformin prescription to have on hand in case I caught Covid.

I’m outraged by the fact that current official guidance on metformin is:

There is insufficient evidence for the COVID-19 Treatment Guidelines Panel to recommend either for or against the use of metformin for the treatment of COVID-19 in nonhospitalized patients.

The scientific literature conclusively shows metformin is safer and more effective than Paxlovid! The cowardly official guidance makes me imagine a counterfactual universe in which I chose to reorient my research program to run an RCT aimed at finding out whether mint can help fight Covid. In the alternate timeline, I gathered overwhelmingly convincing evidence that mint safely and effectively treats Covid, but authorities are still telling everybody they can’t offer any official advice because an infinite treadmill of additional research is needed. Alternate universe Chris Buck might be wrestling with some anger management issues3.

It’s not clear exactly how metformin works against Covid. Metformin can directly block the replication of SARS-CoV-2 in cell culture but only at absurdly high (millimolar) concentrations. The peak concentration of metformin in the blood is a thousand times lower than the concentrations that inhibit virus replication, so there must be something else going on. I note that one of metformin’s many physiological effects is that it can prevent the activation of mast cells (see: “Bullfighting Covid”)

•Mint: A compound called caffeic acid, which is abundant in mint, has been shown to have direct antiviral effects in a cell culture model. Unfortunately, there’s a bit of an in vivo concentration problem along the same lines as antihistamines and metformin. The level at which caffeic acid inhibits SARS-CoV-2 replication in cell culture is about ten times higher than the levels you’d expect to see in the bloodstream after drinking a whole bunch of mint tea. Another problem is that caffeic acid could theoretically act simply by driving the virus into latency, as opposed to permanently eradicating it (see: “Latency, Long Covid, and the Dreaded Rererebound”).

The new possibility I’ve begun entertaining is that mint’s direct antiviral effects in cell culture aren’t at the business end of what makes mint effective in animal models and human clinical trials. I can’t rule out the idea that mint also has antihistamine-like effects or other immune-modifying effects that improve the speed with which the immune system clears the virus.

•Paxlovid: Although the early data from Paxlovid clinical trials led by Pfizer were very encouraging, subsequent trials run by non-Pfizer scientists have mostly found that Paxlovid is of little or possibly no benefit4. The more recent non-Pfizer trials have shown that Paxlovid doesn’t increase the speed at which the infection is cleared, it doesn’t prevent rebound, and it doesn’t prevent long Covid. An attempt to use Paxlovid as a therapy for long Covid showed that it either has no effect or might slightly increase the risk of fatigue and brain fog.

I had initially entertained the hope that starting Paxlovid treatment early and extending the treatment to ten days instead of the usual five would be more effective, but this turned out to be yet another sin against the 15th Commandment. I know four people - including myself - who started Paxlovid immediately after testing positive and continued treatment for 7-10 days. All four of us had rebounds. I’ve become highly skeptical about whether Paxlovid is reliably doing much of anything for anybody. I won’t be bothering with this outrageously expensive and hard-to-obtain drug anymore.

*NO* Tylenol (acetaminophen): taking acetaminophen correlates with worse Covid outcomes. I wonder whether acetaminophen might be doing the opposite of antihistamines - meaning pushing the immune system toward a response that’s less effective for clearing the virus. Aspirin or ibuprofen, which don’t have scary correlations with bad Covid outcomes, seem like safer choices. Although I personally plan to just tough it out and avoid analgesics altogether.

Vaccines: I’m planning to take loratadine (generic Claritin) daily for a week after receiving my next booster dose. A recent paper shows that SARS-CoV-2 Spike directly engages histamine receptor H1 (HRH1)(see: “Bullfighting Covid”). In addition to using HRH1 as an infectious entry receptor, I suspect the virus is engaging histamine receptors for the broader purpose of waving an immune-flummoxing red cape. I’m therefore betting that inhibiting HRH1 signaling after receiving a Spike vaccine could improve my response to the vaccine.

Although azelastine inhibits HRH1, it’s delivered as a nasal spray and only about a third of the dose makes it into circulation. Claritin, which is taken in pill form, seems like a better bet for blocking unwanted HRH1 signaling in the lymph nodes that drain my vaccinated arm. In the future, a testable prediction is that a mutant Spike protein incapable of binding HRH1 would be an intrinsically better vaccine immunogen.

My new thinking about Covid biology makes me prefer mRNA vaccines over Novavax because the mRNA vaccines are better at eliciting killer T cell responses, which I suspect are critically important for bringing the initial infection under control. It doesn’t seem to me that there’s much of a difference between Moderna and Pfizer, in terms of vaccine efficacy. Many people have much worse reactogenicity (feeling like crap the day after the vaccine) with one or the other of the two mRNA vaccines. There’s no indication that reactogenicity correlates with efficacy. Neither of the mRNA vaccines bothers me much, but I imagine other people should choose whichever one doesn’t make them feel like crap.

Regardless of how long it’s been since my last boost, I’ll also plan to get an additional mRNA vaccine booster dose during the first week of any new Covid infection. My theory is that the vaccine in my arm will show T cells the Spike protein in the absence of all the tricks the virus itself is using to flummox the immune response. The properly Spike-educated Th1 cells elicited by the intramuscular vaccine will hypothetically then traffic to my sinuses and bring the infection at least temporarily under control. The post-infection booster dose could also improve neutralizing antibody levels in my blood, which could help ensure the virus can’t spread beyond my sinuses.

My most recent boost targets the XBB.1.5 variant, which first emerged in October of 2022. Things would almost certainly have gone better for me if the boost had contained something more similar to the current FLiRT variant I presumably have. I don’t understand why there isn’t any outrage about the fact that it takes 22 months to make a current-variant boost available when it only took 11 months to develop the original vaccine from scratch. I see the fact that the FDA has us all enrolled in a giant involuntary uncontrolled booster update Tuskegee Study as a causal variable in my Covid ordeal.

•Vitamin D: Although some studies have shown improved clearance of Covid in people given vitamin D supplements, the effects of vitamin D are dizzyingly complex. Amy Proal offers interesting arguments for the view that high dose vitamin D supplementation can have steroid-like immunosuppressive effects, which could theoretically suppress disease symptoms while allowing viruses to replicate out of control. Vitamin D can also exert Th2-skewing effects similar to the “red cape” effects I’m betting Covid exerts.

With all that said, everybody agrees that frank vitamin D deficiency is a disaster. My approach is to get a little sun on long daily exercise walks and to occasionally take a multivitamin with 1000 IU of vitamin D3. I sometimes ask for a vitamin D test at annual physicals and I’ve always been in the middle of the normal range. I note that I’m ridiculously pale.

•Xocova: Clinical trials run by Shionogi, which manufactures an antiviral called Xocova (ensitrelvir), suggest the drug significantly accelerates the clearance of SARS-CoV-2 without rebound effects. Xocova also appears to reduce the risk of long Covid. Xocova has been approved as a safe and effective prescription medicine in Japan since November of 2022. If I’m ever allowed to disenroll from the involuntary Xocova Tuskegee Study, I’ll enthusiastically add it to my treatment regimen. It will also be interesting to find out whether Xocova could be more effective than Paxlovid for treating long Covid.

Yesterday’s post, “Bullfighting Covid,” explores the idea that SARS-CoV-2 is waving a metaphorical red cape that tricks the immune system into thinking it’s fighting worms instead of mounting a more effective antiviral Th1 response. Fortunately for me, vaccination gave me a standing army of properly trained antiviral Th1 cells armed to destroy cells expressing SARS-CoV-2 Spike protein. Although my pre-existing anti-Spike response quickly brought my sinus-localized Covid infection under control, it evidently didn’t fully eradicate the infection because it came back in two separate rebounds over the course of three weeks. The simplest explanation for the rebounds is that SARS-CoV-2 uses a crafty virological trick called latency.

HIV is a familiar story illustrating the principle of latency. Combination antiretroviral therapy can effectively reduce the amount of HIV in a person’s blood to near zero, which effectively reduces the person’s risk of losing all their helper T cells and progressing to AIDS. Unfortunately, HIV is able to temporarily shut off all of its genes and enter a quiet sleeping state in the long-term safehouses provided by resting memory T cells. We haven’t yet come up with a way to eradicate HIV from the resting memory T cell reservoir, so if a person stops taking antiretrovirals then HIV will eventually re-emerge from hiding to rekindle an active infection and resume the inexorable progression toward AIDS1.

In another example, the fact that human papillomaviruses (HPVs) can establish a latent reservoir is why the HPV vaccine only works to prevent infection and can’t eradicate established infections2. The HPV coat protein the vaccine targets isn’t expressed in latently infected cells.

My emerging model is that SARS-CoV-2 has an active state, in which lots of Spike is expressed, and a latent state, where the virus doesn’t express Spike. I imagine that vaccine-elicited anti-Spike T cells repeatedly came in to eradicate all the actively infected cells in my sinuses but the Spike-directed immune response had no way of detecting cells harboring sleeping latent viruses. After my T cells finished cleaning up the Spike mess the immune response went back to a resting standby state. Then a week later the latent SARS-CoV-2 rekindled into an active Spike-expressing rebound infection and rinse lather repeat.

Latency is classically a trick of viruses whose genomes are made of DNA, so it’s important to note that the SARS-CoV-2 genome is made of RNA - which is a lot less stable than the DNA genomes of latent HIV or HPV. It’s good news. While HIV and HPV can trick cellular systems into replicating the viral DNA, the cell doesn’t have any mechanisms for duplicating RNAs. RNA replication is strictly a viral thing. It means that persistent SARS-CoV-2 latency would likely depend on at least occasional expression of the viral “early” genes that maintain the viral RNA by occasionally replicating it at low levels. That means there should be an opportunity for killer T cells or antiviral drugs to find the viral early genes and destroy the latent virus3. It’s a much less challenging form of latency than HIV or HPV.

During my Covid infection, it apparently took my immune system multiple rebounds before I was able to mount an effective response against the early genes expressed in latently infected cells. This was presumably because of Covid’s red capes of histamine flummoxing. I regret that didn’t catch up with the idea of taking azelastine until the beginning of my second rebound. With hindsight, I can imagine the antihistamine had something to do with my immune system finally waking up and smelling the SARS-CoV-2 early-gene coffee.

In the longer run, an obvious way to attack the latency problem would be to incorporate one or more SARS-CoV-2 early genes into Covid vaccines. That way we’d theoretically be able to pre-train a standing army of Th1 cells in the absence of the red capes of a full-blown SARS-CoV-2 infection. A hitch is that nearly all the SARS-CoV-2 early proteins are known to have immune-flummoxing activities - and it’s wise to bet that there are even more flummoxing activities remaining to be discovered. My favorite early-gene target is a protein called papain-like protease (NSP3). I like NSP3 because all its known flummoxing functions are exerted through its ability to chew up other proteins - and I know exactly how to inactivate NSP3’s protein-chewing activity with a single mutation. The sequence of NSP3 is highly conserved - meaning similar NSP3 sequences are found in distantly related coronaviruses. So maybe an NSP3-containing vaccine could also serve as a cure for common cold coronaviruses?

Latency can also explain how SARS-CoV-2 manages to persist in the gut and brain for years, particularly among long Covid patients. Although persistently infected tissues show scattered cells expressing Spike, the latency model predicts the Spike-expressing cells are just the tip of a much larger iceberg. In other words, alongside the detectable Spike-expressing cells there may be many additional cells quietly expressing just enough SARS-CoV-2 early-genes to occasionally replicate the viral RNA. In addition to preventing rebounds, an NSP3-containing vaccine might conceivably be the cure for long Covid?

I’m putting the finishing touches on an upcoming post, “Covid Just Messed with the Wrong Team,” in which I’ll dream big about the idea that a coming age of faster/cheaper vaccine approaches could make it easier for us to experimentally test the predictions of latency hypothesis. And also save the world4.

Today’s story begins with an incident that haunts the nightmares of molecular virologists. In the late 90s, Ronald Jackson and Ian Ramshaw attempted to develop a humane approach to the mouse overpopulation problem in Australia. The idea was to elicit an immune response that would effectively sterilize female mice. The team’s initial attempt used a mousepox engineered to express mouse egg proteins. The approach didn’t work, so Jackson and Ramshaw reasoned that adding an immune signaling flag, in the form of mouse interleuken 4 (IL-4), might improve the immune response against the egg proteins. Since mousepox can’t infect people and mouse IL-4 doesn’t engage human IL-4 receptors, there was no reason to imagine the experiment could be in any way dangerous. However, the results turned out to be surprisingly disturbing. The virus engineered to express IL-4 rapidly killed mouse strains that are ordinarily resistant to mousepox infection. An even scarier observation was that the IL-4 mousepox even killed mice that had previously been vaccinated against the virus.

Bioethicists have spent a lot of time and energy wringing their hands over the question of whether Jackson and Ramshaw should have published their results. I find the question inane. Of course they should have published! While it’s valid to wonder whether a psychopath might see the results as an instruction manual for how to weaponize human poxviruses, the mousepox study is far from the only clue in published literature hinting that IL-4 might make some viruses more dangerous. It was better for Jackson and Ramshaw to tell us what things a terrorist might conceivably dream up so we can start thinking about how to defend ourselves in case of such an attack. More importantly, it’s not just terrorists we have to worry about - evolution is independently cooking up these types of horror stories all the time. One example is Kaposi’s sarcoma herpesvirus, which carries its own natural immune-flummoxing version of IL-6. In the classic wisdom of Laurence Fishburne’s character in Contagion, “Someone doesn't have to weaponize the bird flu. The birds are doing that.”1

Which grimly brings us back to my first Covid infection (see: “The Original Meaning of Quarantine Was Forty Days”). While the Moderna boost I got two weeks before catching Covid obviously didn’t give me magical Wonder Woman bracelets of sterilizing immunity, my vaccination history does appear to have empowered my immune system to keep the infection bottled up only in my sinuses. The question at hand is why my apparently sinus-restricted infection rebounded twice over the course of more than three weeks before I finally cleared the damn thing (assuming there’s not a third rebound still in store for me).

My emerging model for what happened to me starts with the mousepox and KSHV story. What if Covid is promoting an IL-4 or IL-6 dominated response that made it harder for me to mount an effective immune response that can quickly clear the infection. Natural history studies already offer some support for this concept - Covid infection triggers increased IL-4 and IL-6 levels that can last for many months after clearance of the initial acute infection. Also, treating Covid patients with a therapeutic anti-IL-4 antibody called dupilumab results in less severe disease.

It’s important to be aware that the immune system uses different types of responses to fight different types of pathogens. It’s a bit of an oversimplification, but at a very broad level T cell responses can be thought of as divided into T-helper-1 (Th1) and Th2 categories. In general, the two types of helper T cell responses seem to have a see-saw relationship - meaning you generally either mount a Th1 response or a Th2 response against a new infection. Th2 responses, which are coordinated by IL-4 and IL-6 signaling, are thought to have evolved primarily as a defense against parasitic worms2. Classic Th2 responses often involve a type of white blood cell called a mast cell that’s involved in allergic reactions. A signaling chemical called histamine is a hallmark of mast cell activation - and a broad class of drugs called antihistamines are a familiar way to fight this type of response.

We traditionally think of antihistamines as only treating the symptoms of a cold, but the the IL-4 mousepox result makes me wonder: what if sniffling and sneezing are actually just an outward sign that a virus is attempting to flummox the immune system by directing the response toward a worm-fighting Th2 response that’s not very effective for fighting viruses. In that case, suppressing the IL-4/IL-6/allergic/mast cell/histamine response wouldn’t just alleviate symptoms - it could also shift the immune see-saw away from Th2 response and toward a Th1 response that’s more effective for eradicating the underlying viral infection. The idea is that it’s incorrect to simply think about “anti-inflammatory” treatments - you have to instead think about the kinds of inflammation you’re inhibiting or promoting.

To drill down on this idea, let’s geek out on the literature for a specific over-the-counter antihistamine called azelastine (brand name Astepro). Early in the pandemic, surveys of medical records detected an intriguing correlational trend in which people with prescriptions for many common allergy medicines were found to be less likely to test positive for Covid. People with azelastine prescriptions seemed particularly unlikely to have positive Covid test results on file. The observation led to a number of randomized controlled trials, all of which found that people given antihistamines show faster resolution of Covid symptoms compared to people given a placebo.

In one study, azelastine promoted faster disappearance of Covid symptoms while also promoting faster disappearance of virus in nasal swabs. A recent paper offers a possible explanation for this result by showing that SARS-CoV-2 can use azelastine’s target, a cell surface protein called histamine receptor H1 (HRH1), as an infectious entry receptor. Azelastine prevents SARS-CoV-2 from using HRH1 to infect cells. At face value, this appears to tie a tidy bow on the story of how azelastine promotes faster clearance of the virus, but there’s a hidden problem with the inference. The concentration of azelastine required to suppress SARS-CoV-2 infection in cell culture is a thousand times higher than the peak concentration of azelastine in circulation. Since azelastine never approaches the concentrations required for direct inhibition of viral replication in vivo, there must be something else going on behind the scenes. My bet is that SARS-CoV-2 Spike is directly triggering HRH1 signaling and azelastine is effective in vivo because it counteracts the false histamine signal. If we imagine SARS-CoV-2 as a matador then azelastine is effectively removing one of the virus’s Th2 red capes - in a way that helps the immune system mount a proper Th1 response that can clear the virus more quickly.

Another example to drill down on is famotidine - a familiar antacid that goes by the brand name Pepcid. Famotidine targets histamine receptor H2 (HRH2). Unlike HRH1, which is abundant in the nasal mucosa, HRH2 is abundant in the gut. Famotidine was one of the first “repurposed” drugs to show clinical efficacy against Covid, including efficacy against neurological symptoms. Famotidine, like azelastine, reduces SARS-CoV-2 viral load in Covid patients. In contrast to azelastine, a series of papers have ruled out the possibility that famotidine exerts direct antiviral effects in cell culture systems. It again seems that the most likely explanation is that famotidine is working by removing the red cape of Th2 flummoxing.

A number of supplement products have crossed my radar as having convincing Covid-fighting effects in clinical trials. Now that I’m looking through the Th2 lens, I realize that curcumin, melatonin, and quercetin have all been implicated in suppressing things like mast cell activity. Another promising Covid treatment, metformin, has a dizzyingly wide range of metabolic effects, but one of its known activities is suppression of mast cell activation. If you drill down on the C19early.org summary of the diverse range of interventions with evidence of efficacy for treating Covid, a large majority of them suppress IL-4/IL-6 signaling. It’s very suspicious.

In summary, the idea that has been swimming up through the murk in my mind is that we may have been missing a unified field theory of Covid drug repurposing. Anything we can get our hands on that inhibits IL-4-related pathways suddenly seems like an interesting candidate for fighting Covid because drugs and supplements in this category could help shift the immune response in a more productive direction that doesn’t merely clear the virus faster, but could also help lay down a better immune memory that protects people against repeat Covid infection in the future. And it’s not just Covid - it’s conceivable that other pathogens are using IL-4/IL-6 pathways as a red cape too.

There are a bewilderingly large number of drugs and supplements to consider in the Th2-antagonist category, and it’s very frustrating to realize that the effects I’m invoking won’t be detectable in standard lab assays aimed at measuring direct antiviral activity in cell culture. The theory suggests we’re doomed to investigate this kind of thing in the real world in actual humans. Consumer Reports for Medicine! Now!