Coronavirus news & views

Tattoos and Vaccines: Muddled Thinking And A Good Idea

“Often wrong, never in doubt”  Anonymous

Muddled thinking. Despite reams of evidence to the contrary, including a recent Nobel Prize for the technology, vaccine fabulists, like RFK, Jr, , Robert De Niro, Jenny McCarthy, my own Senator Ron Johnson, and too many others continue to spread intentional disinformation about the safety and efficacy of the COVID mRNA vaccines. Despite these naysayers, mRNA vaccines are here to stay and new ones are being developed for many other maladies that have been hard to vaccinate for, like cancer, HIV, several animal diseases, etc.

I keep encountering people who belabor the same old disproven canards about millions of people falling dead from the vaccines, about the vaccines being “experimental,” and “gene therapy.” All this disinformation continues despite the fact that tens of billions of jabs have been given to 5.6 billion vax recipients around the world over the last 4+ years. At what point does  fact replace lie and truth supplant fable? The world’s entire medical establishment does not agree with these deceivers, yet they continue to sound the sham anti-vax alarm undaunted. I have pondered in these pages whether this willful dissemination of such disinformation that could affect peoples’ lives and health could be criminal. A case for this could be made.

The funny thing is that these alarmists are announcing the sky is falling over something well tested and vetted while ignoring another very common jab that many of them have likely have gotten without questioning, but that does have significant effects on one’s immune system: tattoos (see vocal anti-vaxer and celebrated tattoo artist, Kat Von D). When you stick hundreds of ink-filled needles into your skin, can it be good for you? Anti-vaxers worry about well tested and vetted vaccines, but never worry about tattoos. Why their selective outrage?

Much of tattooing remains mysterious: Scientists aren’t fully sure what makes certain tattoos fade fast, why others stick around when they’re supposed to disappear, or how they react to light. Given the fact that tat recipients are sitting for multiple injections of unknown substances into their bodies that last forever, tattooing would seem like a much better way than vaccines for someone like Bill Gates to poison us; or to use them for something sinister like mind control, or as a way to control the world population, as the vax chicken-littles often frett about with the mRNA vaccines. Why aren’t folks up in arms over this vast potential conspiracy? (Cynicism mine!)

What do tattoos do? The Atlantic recently ran an article about how tats mess with the immune system and a subsequent quick search found other concerning aspects about them. The practice involves poking dozens to thousands of holes into the middle layer of the skin, or dermis, and depositing different formulations of chemicals, or pigments, that permanently remain behind. Contrast that to the single shot of a typical vaccine that deposits into a muscle a single dose of an agent that has undergone extensive testing and approval for safety and that quickly is eliminated by the natural scavenger cells and processes of the body’s immune system so nothing remains soon after the shot is given. Both procedures irritate the immune system, but one is permanent, the other temporary.

When the hundreds of needle pricks deposit ink into the dermis for a tat, the immune system detects an assault on its body and jumps into action. The skin after all, is our immune system’s first barrier and it is well loaded with rapid-response defensive cells that lead the assault on the pigment intruder. This generally works well to heal wounds and clear infections, but the system breaks down trying to fight tat ink. The immune system simply cannot adequately clear that intruder. Rather, the pigments persist in the belly of the immune cells and skin cells, only to again be gobbled up when those cells die and disgorge their undigested contents. Then the process repeats, ad nauseam leaving a permanent stain in the skin.

Over time, the edges of tats fray and become fuzzy as ink particles are gradually shuttled away into the draining lymph nodes, which normally handle viruses, bacteria, fungi, etc. In the nodes, the immune system then revs up to recruit and deliver antibodies and T cells around the body to combat intruders that escape further into the interior. These nodes normally are pale white, but in tattooed people, they can be the color of the tattoo ink.

Thus not only is the skin tattooed, so are the lymph nodes!

It is not clear if all this misdirected immune response to tattoo ink throws the immune system off its game of surveillance against infectious pathogens. One study published last year found that tat ink can affect the function of immune cells. But, in another Australian study, tat ink was mixed with a vaccine in order to track the fate of the vaccine components after vaccination. There was no evidence of any untoward effect of the pigment on the vaccine itself. Other immunological differences between heavily tattooed and un-tattooed people have been noted but it remains unclear whether these are for the better or the worse. So, it remains uncertain whether tattoos are good or bad for one’s immune system.

However, tat ink can be harmful in other ways. The European Union banned certain pigments, that they believe are linked to bladder cancer. And a 2016 report from the Australian government found that >80% of black inks contained carcinogenic polycyclic aromatic hydrocarbons (PAHs). Other pigments may contain other harmful substances like barium, cadmium, lead, mercury, micro-plastics, etc. Then there always is the real risk of infection or allergic reaction when anything is injected into your body. Nice.

Tattoo-like vaccines: a good idea. In a typical vaccine, the shot is delivered into an arm muscle where the immune system is not as robust as in the skin. The skin being a primary barrier to a hostile outside world is well stocked with an armament of immune sentry cells, muscles deeper in the arm not so much. But, there are enough immune cells in muscles to get the job done and develop protective immunity to antigens which the vax delivers. For an intramuscular vaccine delivered to an arm muscle, usually a comparatively large antigen dose is used and it takes a bit of time to get the immune system in gear. Mobile immune cell cops where the vaccine bolus is deposited gobble up the material like a squirrel shovels nuts in its mouth, and then head to nearby lymph nodes to “report” that an intruder was encountered. This gets the army of T and B lymphocytes ginned up and pumping out antibodies, other immune molecules and cytokines, and other cells to respond the intruder. You are then “immunized.” This also sometimes causes the temporary malaise associated with vaccines—mild fever, fatigue, flu-like symptoms and maybe arm pain. In rare cases, allergies happen, which is a rapidly arising, acute immune response to a component in the vaccine, such as chicken egg material found in many, but not all, flu vaccines. 

However, a few vaccines are actually given in the skin, more like tattoos are administered. Currently this route is used to vaccinate for small pox, TB, rabies, and more recently, mpox (formerly called monkey pox). Some studies, but not all, have shown that the intradermal (ID) vaccine route can outperform the intramuscular (IM) vax route. For this reason, other vaccines are now being developed to be given this way simply because the skin immune system is more robust and this might provide a more effective way to vaccinate, and it uses less vaccine material. This is called intradermal vaccination.

But intradermal (ID) vaccines are not that easy to administer. If not done properly and the vax material is injected too deep, which is easy to do, their efficacy can drop precipitously, just like Biden’s presidential chances plummeted after the disastrous debate. So, medical folk are actually looking at different vaccine technologies, including using tattoo machines to administer effective ID vaxes on a large scale across many clinics large and small. One technique using a DNA vaccine, called DNA tattooing has been tested in animal models and human trials and was inspired by traditional tattoo machines, which are pretty easy to use.

Bottom line: The way that vaccinologists have taken notice of tattoo technology to improve vaccine efficacy is intriguing. They have taken their science knowledge of skin immunology and realized that the pop culture tattoo fad just might improve vaccine technology and public health. That is very cool.

The sad irony is that many people who get tattooed are also vax deniers. Their cognitive dissonance is disturbing. Vax deniers loudly spread disinformation about vaccine dangers, then are completely sanguine about tattoos which inject strange chemicals into their bodies, some of which have been clearly proven to be unhealthy.

That selective outrage betrays the intellectual dishonesty and lack of curiosity of anti-vaccine dissemblers. Too bad we can't vaccinate against that.

Acknowledgment: I am indebted to Frank C. (no relation) for helping procure an article needed to write this blog post, which I had a very hard time accessing without paying a full subscription to the journal. Thanks Frank!

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

BioX Wins The Nobel!

“If you start to take Vienna, take Vienna”— Napoleon (reportedly)

What’s the fuss? BioX won the Nobel Prize….er rather it was the mRNA vaccine that won. Correction—it was the scientists, Katalin Karikó and Drew Weissman of the University of Pennsylvania, who developed the RNA technology that went into the novel vaccine who won the prize. But their work directly led to the vaccine, a first fruit of BioX.

Readers of these blog pages might remember that about this time in 2020, that year’s Nobel award for Medicine or Physiology went to three scientists for their decades-long search to discover what caused hepatitis type non-A, non-B. It turned out to be a whole new virus, the hepatitis C virus (or HCV) that took four decades to identify. Even though it still remains a huge health problem, there still is no vaccine for it. I compared that four decade slog just to find the pathogen to how fast the novel viral cause of COVID-19 was found and a vaccine developed—all done in less than a year! I anointed the new biology that did that amazing feat, ‘BioX.’ That was rather prescient of me, since three years later, the co-founders of the COVID vaccine using BioX too were awarded the Nobel Prize.

I dubbed the new amazing post-molecular biology science that enabled such a quick identification of the novel coronavirus and development of a vaccine against it, ‘BioX’ after SpaceX. SpaceX, of course, is the name for the new way space travel is now being done. Shortly before the Nobel award for the discovery of HCV, Elon Musk’s SpaceX took astronauts in an unpiloted vehicle to the International Space Station. Then the launch vehicle, rather than being discarded as usual, was landed, upright, in the center of a bullseye on a barge off the coast of Ireland, to be reused on a future space flight--maybe to Mars? The whole thing was developed in a fraction of the time at a fraction of the cost of what NASA had historically been doing. NASA’s technology was rendered archaic by SpaceX, which introduced us to a new era of space travel.

The breathtaking speed with which a new biology discovered the SARS-CoV-2 virus and then developed a safe and effective vaccine against it ushered in a new post-molecular biology world I dubbed ‘BioX’.

Now the details. But as breathtaking as SpaceX is, it was not developed overnight in a vacuum. It arose on the back of decades of NASA engineering R&D, which included some spectacular failures and even a few tragic deaths. Similarly, as breathtaking as BioX was with the rapid identification of a novel virus and development of the new mRNA vaccines to a wholly new disease, that technology too was built on the back of decades of hard work, punctuated with many failures, but also flavored with impressive perseverance on the part of a few individuals.

There are two major components to the novel COVID vaccines—the mRNA which generates the viral protein to which the immune response is made, and the lipid nanoparticles that encapsulate and protects the fragile mRNA from a world that is hostile to mRNA. Both components took very separate, decades long, twisting, uphill roads to develop. Both nearly met with failure. And both came together with spectacular success. BioX!

• The mRNA. Weissman, and especially Karikó, languished for years on the fringes of science with a, then, very weird idea of using mRNA to produce drugs or vaccines. Their collaboration began with a chance encounter at a UPenn copy machine in the 90s and went downhill from there as recently told in the Wall Street Jounal. Funding for their work was hard to come by. Karikó was banished to an office on the outskirts of the campus and languished in a non-faculty position for years. At one point, she had to take a demotion to simply keep a job at Penn.

They just could not get their idea to work. The mRNA was too fragile and too short-lived to work with and produce the desired proteins when they tried to express it in cells or animals. The fact is that there are ubiquitous enzymes all around us called RNases that have a ravenous appetite for mRNA. RNA molecules, especially mRNA disappear almost as fast as one can purify or make them, let alone then try to get them into cells in tissue culture or into bodies. On top of that, when naked mRNA is injected into a body, it elicits a powerful immune response that further quickly degrades it. Note that there are several different types of RNA, and mRNA is the most fragile and hardest to work with, but it is the type that provides the message that turns a genetic code into a protein molecule like a spike protein, which is why it is used in the vaccine.

The researchers had great difficulty getting grant funding for their research because no one believed it would go anywhere. When they could produce some data, they had a very hard time finding journals to publish it. No one was interested because no one believe that there was any utility in the whole premise of using mRNA as a therapeutic tool. In the publish-or-perish world of academia, such negative peer pressure usually is the kiss of death. They should have seen the writing on the wall and been teaching high school biology. But for some reason, Karikó continued to have faith in her idea even though no one else did. For some reason, she persevered.

After dogged determination and ignoring all the naysayers, she eventually had a major breakthrough after a doing a simple experiment. They found a simple way to protect the mRNA from the immune response and published this in 2005. It opened the field and colleagues minds about using mRNA as a possible therapeutic tool. But there still was the problem that mRNA was exquisitely sensitive to RNase enzymes that were everywhere—on your fingers, in your breath and blood, even on sterilized surfaces—the enzymes are incredibly stable molecules and very hard to destroy. Life intended mRNA to be short lived molecules, not to be used in vaccines.

It wasn’t until folks paired the immune-stable mRNA of Karikó and Weissman with a way to protect the molecules from RNase enzymes that mRNA vaccines became possible so they could win the Nobel Prize. Lipid nanoparticles did the trick.

• The lipid nanoparticles. The story behind the development of the lipid nanoparticles used to deliver the CoV-2 viral spike mRNA sequence to cells so they could use their normal gene expression machinery to put the spike protein on their surface and generate an immune response is a long one. In that regard it is quite similar to the long, arduous story behind the development of the therapeutic mRNA. Early on, neither technology was believed possible or useful by the scientists’ peers. Both groups had very hard times getting their scientific feet on the ground. Both nearly failed. I described Karikó’s struggle above and in March 2021 I wrote in these pages about the professional plight of Bob Langer who, in the 70s, had a vision for using liposomes (short for lipid nanoparticles) for delivering fragile bio-molecules and drugs to cells (you can read that post here). Briefly, his idea was to create mini-cells in which to package and protect fragile therapeutic molecules and then deliver them to cells and tissues in the body. The liposomes containing the fragile therapeutic molecules would fuse with the lipid membranes of cells and disgorge their contents into the cells. Many people told him it was not possible and he had his first nine grant applications rejected—and this was a time when medical science research grants were easy to get (when I was in graduate school in the early 80s, NIH grant applications had a 50% success rate. By the time I became a faculty member in the late 80s that dropped to 10%). Langer, like Karikó, also could not get a faculty position because people did not believe in his research. Also like Karikó, for some reason Langer persevered.

Also like Karikó, Langer too succeeded—eventually. It took a long time. The technology he successfully developed was first used to package a drug used to treat a rare genetic disease that causes nerve and heart damage. It also was used to package mRNA for an Ebola vaccine. From an ignominious beginning, Bob Langer became a professor at MIT where there now is a bioengineering lab named after him. That is not quite as nice as winning a Nobel prize, but high recognition still.

Along the way, he also co-founded a small biotech company named Moderna that was focused on developing mRNA vaccines for infectious diseases, cancer and other diseases. Then COVID came calling and Moderna immediately pivoted, and along with BioNTech, NIH, and Pfizer, quickly gave us mRNA vaccines delivered in liposomes that saved millions of lives from COVID.

That is how BioX technology led to the Nobel prize this year.

The bottom line. BioX, like SpaceX, was built on decades of hard research that was punctuated by painful failures, but highlighted by dogged determination. Both technologies, BioX and SpaceX, are here to stay at least until the next amazing thing replaces them. You can bet that that next amazing thing will have been developed on the back of determined researchers who very possibly will be working at the fringe of their professions and may flirt with professional failure early on. You can also bet that the next amazing things will be built on the backbone of SpaceX and BioX. That is how science and engineering painfully progresses.

So, when you hear someone say that the mRNA vaccines are experimental like I very often do, tell them the truth. They were built on decades of hard research going back to the 70s.

Stay tuned for a coming post on the future of BioX, which is here to stay for a while. New mRNA vaccines are being developed for previously vaccine-impossible diseases including HIV, cancer, and various animal diseases. Work also is underway for a universal flu vaccine.

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.