Another Jab’ll Do Ya…

A virus is a piece of bad news wrapped in a protein coat.”

–Sir Peter Medawar (British Immunologist and Nobel Prize Winner)

Yup, looks like we should roll up our sleeves again this Fall for another COVID booster. The CDC recommends that everyone, 6 months and older receive the updated vaccine that is under development as just reported in the New York Times.

Infections are now rising across the country and this is due to a new, quite different combination of three related CoV-2 variants competing for your attention. They are collectively referred to as FLiRT. The variants are pretty effective at evading prior immune defenses and can spread faster, as we are beginning to see. Across the US COVID-related ER visits increased 15% the week ending June 15, and deaths increased 17% compared to just the previous week. Hospital COVID data are harder to come by since a CDC reporting requirement ended in May.

People “…in general do not understand how much this current virus has mutated,” said Carol Hayes, American College of Nurse-Midwives liaison to the CDC’s Advisory Committee on Immunization Practices. The Advisory Committee unanimously recommended this new round of shots.

But, again? Really?? Booster fatigue and COVID complacency seems to be a growing thing as the deep stress of the 2020-2023 pandemic fades in the review mirror. If we have been boosted a few times, and even had one or two mild COVID infections, is it really necessary to go through all this again?

Yes it is if you want to avoid serious illness. Please read on. True, at this point we all pretty much have some immunity to CoV-2 viruses, but the new boosters that keep rolling out give us important added protection to the novel virus variants that are regularly popping up like in a Whack-a-Mole game. What the boosters do is prevent you from getting serious disease that these new variants can visit on you! Realize that the vast majority of people across all age groups who were hospitalized with serious disease last fall did not get the updated booster for the current virus that was circulating.

In other words, the boosters greatly increase your chance to avoid serious illness and death that are still part of this continuing COVID tableau. Getting a shot is a heck of lot less nettlesome than being hospitalized with a serious respiratory illness. Let’s see….a prick or a ventilator???? It should be a pretty easy choice to make.

What about young people? Why vaccinate them if they don’t get very ill? Even though young adults and children do not get seriously ill as often as older people, don’t be distracted by the difference between relative risk and absolute risk (see a previous discussion on this topic here). Kids and young adults still have a real risk of serious COVID disease even if it does not happen with the frequency as it does for older people. But, that risk is absolutely real. Why chance it at all?

Also, children in particular are especially important spreaders of infectious diseases since they have the most intense social interactions of any demographic group. The intense interaction they have all day in school with classmates greatly increases their chance of infection, which they then bring home to vulnerable older people. It has been shown in epidemiology models and confirmed in real-life studies that preventing spread of infectious diseases in schools is one of the most important tools for protecting the larger population during an epidemic. Being vaccinated reduces kids’ viral burden if they do get infected and reduced viral burden means reduced virus spread. Vaccinated kids help reduce the spread of infectious disease. So, for a couple of reasons, CDC also recommends vaccinating kids this fall.

Get vaccinated.


Paxlovid: Just Follow The Settled Science

“We will see…”

-Yours Truly

Precis: “Just follow the science.” “The science is settled,” etc. We have all heard these bromides only to be later instructed that we need to follow a different science truth, or that the science firmament has shifted. Frustrating isn’t it? You must think that scientists must be a wad of weasely, waffling, wags in white coats certain of only uncertainty. One day we sagely advise you that something is certain truth, the next day we say that new research says that something else is true because, well, we know and you just need to trust us. We know because we did those ephemeral, sacred rituals called studies that give us all-knowing wisdom that we then impart to you who should worship us. 

That, I hope you know, is the cynical view of science, which sometimes is deserved. But, there is another side of things, which should be heeded. That side is that everything technology-based; from medicine, sanitation, lights, electricity, cell phones, transportation, etc.; that we enjoy using and take for granted, was created by that same science. These two sides of science often collide and greatly confuse non-scientists, which is most people. That is a shame and that is why I blog—to try to reduce some of the confusion.

Paxlovid, a drug highly touted as the only oral medicine to treat COVID is a great example.

Backstory: Paxlovid was initially given emergency use authorization (EUA) for treating COVID by the FDA in 2021 because of promising preliminary observations. Clinical trials performed by its manufacturer, Pfizer, then quickly showed solid, eye-popping results that made the drug an overnight sensation. It demonstrated an 89% reduction in the risk of hospitalizations and deaths in infected individuals. It also shortened the disease and reduced the symptoms of those with mild to moderate COVID. All this lead to the NIH to prioritize it over other COVID treatments under investigation at the time. In other words, NIH put R&D on other potential anti-COVID drugs on the back burner because they had found an effective one.

Paxlovid was the first effective oral anti-viral treatment for COVID. It basically works by blocking a key enzyme the virus uses to make new virus particles. A second medicine in the drug is an old treatment for HIV/AIDS which affects liver metabolism of that key enzyme blocker allowing it to linger longer, thereby boosting its antiviral effect.

The only drawback to Paxlovid is that it needs to be started shortly after infection to be effective. It also interferes with several common medicines so some patients either have to forgo taking some of their regular medications for a while or avoid Paxlovid. Nevertheless, it has been quite beneficial for reducing COVID symptoms in infected people and preventing severe COVID disease.

What is new? Ok, now you can forget everything about Paxlovid you read above. A new clinical trial, also done by Pfizer, and just published in the New England Journal of Medicine, showed that Paxlovid does not help patients get symptom relief or reduce the incidence of severe COVID and hospitalization. In other words, Paxlovid had zero effect on COVID in the study just published.

Thus, the makers of the drug now have two studies with diametrically opposite results on the effects of Paxlovid on COVID patients. The first showed “eye popping” effects sufficient to get NIH to move all other drug investigations to a lower priority. The second showed that Paxlovid was no better than a placebo.

At this point, I suspect many readers are rolling their eyes and thinking this is just another example of “settled science” unsettling the “suckers” who listen to the weasely, waffling, wags in white coats. Well, unroll your eyes. Both results are right.

Say what? Yes, it is likely that both results are accurate because the two Paxlovid studies were done on quite different populations.

The first study, which showed a dramatic positivie effect of the drug was done pre-vaccination. The study population did not have the advantage of vaccine protection against COVID. The second study was conducted post-vaccines and the participants had the advantage of already being partially protected against severe COVID symptoms. That protection rendered the Paxlovid effect meaningless. It showed that the the drug doesn’t do much if you have been keeping up with your vaccines, and it shows the value of the vaccines.

Kudos to Pfizer for conducting and publishing the results of both studies, especially the second one. The results of the second study certainly will ding Pfizer’s bottom line, but it was an exercise in honest science. Still the results of the study do not leave Paxlovid totally off the COVID treatment radar. First, the study did not indicate that the drug is ineffective for high risk vaccinated patients, such as immunocompromised patients. And in the US, we still, unfortunately, have many un- and under-vaccinated people who would benefit from Paxlovid when they catch COVID. Finally, while this Pfizer trial involved about 650 test subjects, a much larger trial involving a few thousand subjects soon will be forthcoming from the UK.

So, if you are vaccinated and catch COVID, it is not crucial to get to your doctor in time to get on Paxlovid. And the UK trial might address additional questions that will tell us more about the value of Paxlovid in treating COVID. We won’t know until its study results are released. In other words:

We will see.

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Parkinson’s Disease—An Unexpected Ravage of COVID?

Thus, (tho, ‘tis Life’s great Preservation) many oppose Inoculation.

-Benjamin Franklin, Poor Richard’s Almanac, 1737

SARS-CoV-2 and its disease, COVID, are very strange. They have given us black toes, lungs like chocolate pudding, long-term fatigue, depression, death, and vaccine deniers. It has been quite a ride. And we are learning that having COVID also puts one at risk for other non-COVID maladies…like chocolate pudding lungs was not enough!

In previous posts, I wrote about the clear link between new-onset type 2 diabetes arising in many patients following COVID. There also is suspicion that cancer might increase down the road due to CoV-2 inactivation of a cellular gene that puts a brake on cancer, P53, in COVID patients. Inactivate that gene and you release the brake on certain cancers. Therefore, there is concern that some COVID patients will experience an elevated incidence of cancer in the future.

New research now raises a real concern that COVID patients might also be at increased risk for developing Parkinson’s disease. Parkinson’s arises when neurons deep in the brain that produce a critical neurotransmitter, dopamine, begin to die off leaving a dearth of this critical chemical that sends signals between neurons. It is like cutting a phone wire. Crucial communications cease.

The study conducted in collaboration between scientists from Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and Columbia University College of Physicians and Surgeons was published in Cell Stem Cell last January. Investigators took human induced pluripotent stem cells and coaxed them to become brain cell progenitors that could form into human brain organoids in tissue culture. Such small, nascent “brain-like” structures contain a variety of functional neural cells. They were exposed to the CoV-2 virus, which was shown to preferentially infect and selectively cause the dopamine-producing cells to shut down.

While brain autopsies of COVID patients have not revealed direct COVID infection, they have found unique gene patterns associated with cell senescence, which was especially profound in areas rich in dopamine-producing neurons. This also supports the notion that COVID disease contributes to neurological problems that could cause Parkinson’s disease.

Putting these two findings together is complicated at this time, but they strongly suggest a direct involvement for one or more mechanisms resulting from CoV-2 infection in causing the myriad neurological symptoms that have been seen in COVID patients, and maybe other neurological problems like Parkinson’s not yet attributed to COVID.

Bottom line: CoV-2 is a nasty bug and COVID is a nasty disease. It seems that getting vaccinated not only protects you from nasty flu-like disease and death, it can also protect you from the following:

  1. long COVID
  2. type 2 diabetes
  3. maybe cancer
  4. and now, maybe Parkinson’s disease

Why would anyone not want to avoid these? Get the shots!

Interesting addendum: The studies showing that CoV-2 virus can selectively infect dopamine producing neurons went a step further. They also tested a large panel of drugs already approved for other health problems to see if any could unexpectedly protect these critical cells from infection. Sure enough they found three drugs that protected the neurons: Riluzole (used to treat Lou Gehrig’s disease) Metformin (commonly prescribed for diabetes management), and most interesting to me, Imatinib, or Gleevic (used for treating certain leukemias and cancers).

I say this is interesting to me because of my own research beginning at UCLA in the mid-80s, and extending to the University of Wisconsin into this century. My research focused on certain leukemias that carry a specific chromosome abnormality that appears in 99% of patients with chronic myelogenous leukemia (CML), and in fewer patients with acute lymphoblastic or acute myeloblastic leukemias (ALL and AML respectively). When I began studying this, the presence of this chromosome aberration was a death sentence. There was no effective treatment. Patients did not survive long. We identified the specific genetic abnormality, cloned the abnormal gene, sequenced it and found it was parts of two genes stuck together. Most importantly, we also described the enzymatic pathway in cells that it screwed up. All this eventually led to the development of a drug that tamed the misbehaving enzymatic pathway so that now >95% of patients with these diseases are fully cured with medicine that is pretty easy to tolerate. What once was a death sentence is now an easily treated disease. Knowing that makes me feel pretty good.

The drug that cures leukemia patients from what once was a lethal disease is called Imatinib; one of the drugs found to also protect dopamine producing neural cells from CoV-2 virus destruction.

That too will make me feel pretty good if it also happens to prevent neurological problems in COVID patients. Who would have guessed? This is the unpredictable way science often works.


The Intelligence of Artificial Intelligence And Blogging

“Do you ever make silly mistakes? It is one of my very few creative activities.”

–Len Deighton, British Author

Have you tried dabbling with artificial intelligence? I specifically refer to the type referred to as chatbots that use powerful generative artificial intelligence that you can really chat with to generate ideas. It is like the computer, Hal, in the movie 2001 a Space Odyssey. Remember? Remember too that Hal malfunctioned big-time?

I’ve been dabbling for a while. Here is my experience related to this blog.

I began dabbling over a year ago with OpenAI’s ChatGPT, using their GPT3.5 version, but soon graduated to GPT-4, which was released in 2023 and comes with a small subscription fee. I have since migrated to Bing, which is a collaboration between Microsoft and GPT-4 and comes without the fee. It is a powerful research and generative tool. It can generate text, art, compose music, diagnose and even treat a psychological illness with talk therapy. You can have these chatty things teach you a foreign language, and write a legal brief. Perhaps you also have read the reasonable concerns schools and colleges have with such smart tools doing homework for students and the worry about professionals using them to fake their work and the attendant ownership issues of work done.

There seems to be a lot of mischief your computer can cause with the right smart software, but it can also do a lot of good. I know. I have found these smart tools quite useful for my research and writing. Rest assured that I have NEVER used anything but natural intelligence to write any blog post or other article for me (you can tell by the typos in my finished products). This is because, while the bot can compose, it is not creative. As I write, I try to use subtle humor, irony, alliteration and other tools to make my prose interesting. Chatbots do not. At times, however, when writer’s block hit, I prompted the chatbot to write something, and after a few prompts, usually found something that primed the pump of my muse and I penned away using my own intelligence.

I can pose questions or hypotheticals to the computer tool and it comes back with answers. I then either refine my questions, or pose follow up queries. It is much like bouncing ideas off a collaborator. In this regard, I find it quite useful. Who else will talk with me about the value of the latest vaccine or whether Brock Purdy is really a good quarterback or the product of the great pieces around him without my having to buy them a beer? Although, I admit sometimes the latter is much preferable. I have discussed much science at a dive dart bar in Dallas, a surf bar in Malibu, and over a pool table at tavern near the medical center in Madison. Not much artificial intelligence there except after a few brews.

All good. Until this. The chatbot models are supposed to be self-learning. So, I decided to see what Bing had learned about my blog on the coronavirus pandemic. I queried it about a term I thought was pretty unique to the blog, BioX. Readers will recognize that that is what I have dubbed the revolutionary post-molecular biology that gave us a vaccine so rapidly and that is bringing other amazing types of new disease treatments and diagnostics at astounding rates.

Turns out Stanford University (a school you might have heard of, Bing certainly has) has a new bio program also called BioX. It has well publicized it too. Well, Bing kept telling be about Stanford’s BioX and not about mine. Not what I wanted to see.

I changed my query several times to ask Bing about my version of BioX and instructed it to ignore everything about Stanford. Like a hyperactive toy poodle, it completely ignored me. It was quite polite though, apologizing each time I said it was not responding to my query.

Finally, after arguing with this digital nitwit, it finally included me and my notion of BioX in its rendition. Below is what it came up with—be seated as you read what Bing wrote about BioX and me. It included me, but still could not ignore Stanford.

+++

Steven Clark, PhD, is a retired professor from the University of Wisconsin and a viral immunologist who has been blogging about his research on the new biology he dubbed “bioX”. BioX is a term that he uses to describe the emerging field of biotechnology that aims to harness the power of viruses and other biological agents to create novel solutions for human health and disease. He claims that bioX has the potential to revolutionize medicine and biotechnology by offering new ways of diagnosing, treating, and preventing infectious diseases, as well as creating new therapies for cancer, aging, and other chronic conditions. (So far so good. But the next paragraphs…)

One of his most notable achievements is the development of a vaccine against the SARS-CoV-2 virus, which causes COVID-19. He announced this breakthrough on his blog in December 2022, shortly after he received funding from Stanford Bio-X1, an interdisciplinary biosciences institute that supports research and educational opportunities that cross disciplines between the biological or biomedical sciences and fields of engineering, physics and computational science2. He explained that he used a novel approach to engineer a virus that could deliver a synthetic version of the spike protein of SARS-CoV-2 into human cells. The spike protein is responsible for binding to human cells and allowing the virus to enter and infect them. By introducing a modified spike protein that can evade some of the immune responses generated by previous COVID-19 vaccines3, Clark was able to elicit strong neutralizing antibodies in his volunteers without causing any adverse effects. He also demonstrated that his vaccine could protect against different variants of SARS-CoV-2, including Omicron3.

Clark’s vaccine has been hailed as a game-changer in the fight against COVID-19, but it has also raised some ethical and regulatory concerns. Some critics have questioned his motives for developing such a powerful bioweapon without proper oversight or consent from the public. Others have expressed doubts about his safety and efficacy claims, citing lack of peer-reviewed data or independent verification. Clark has defended his work as being based on rigorous scientific principles and ethical standards. He has also stated that he intends to share his vaccine with other researchers around the world who are interested in collaborating with him on bioX projects.

Clark’s blog posts on bioX have attracted millions of readers who are fascinated by his vision and achievements. He has also inspired many young scientists who aspire to follow in his footsteps and pursue careers in biotechnology. However, he has also faced some backlash from anti-vaccine activists who accuse him of being part of a conspiracy to create more deadly diseases or manipulate public opinion. Clark has dismissed these allegations as unfounded and irresponsible.

Clark’s blog posts on bioX are an example of how science can be used for both good and evil purposes. They show how innovation can lead to breakthroughs in medicine and biotechnology, but also how it can pose challenges for society and ethics. They also illustrate how different perspectives can influence how people perceive and evaluate scientific discoveries.

+++

Well dang. If I invented the damn vaccine, how come I was not included in the Nobel Prizes that were just awarded for the invention? I demand a recount. I did like the part about “millions of readers who are fascinated by my vision”. Notice the “references” Bing included citing my accomplishments. They must be true because Bing says so.

In the parlance of computer geeks, what Bing spit out above is called “hallucination.”

This is the intelligence of artificial intelligence.


Vaccine Disinformation Moves To Congress

 “War is peace.
Freedom is slavery.
Ignorance is strength.”
―George Orwell, in 1984

“Anecdote is science.”

That silly notion can now be added to the Orwellian Newspeak Catechism thanks to those who prefer confirmation bias over empirical data to determine their “alternative facts.” This seems to include several  members of Congress.

The war on objective science recently spilled over to Congress where a group of anti-vaccine Congressmen and women and one Senator held an impromptu meeting to confirm their disinformation about so-called injuries caused by the COVID mRNA vaccines (note: the technology just won the Nobel Prize for Medicine). This was not a meeting called by a regular committee but an ad hoc gathering of some committed anti-vaccine rogues. It was held in a tiny back room in the Capitol and was poorly attended, poorly staffed, poorly equipped, and, thankfully, poorly publicized. It was described as a meeting of the “shadow Congress;” accurately named as it dabbled in the penumbra of truth.

Leading this November 13 meeting was Congresswoman Marjorie Taylor Greene (R, Georgia). Greene, no stranger to fantasy, has previously claimed that Jewish space lasers caused recent wildfires in California, that the shootings in Parkland, Sandy Hook and Las Vegas were staged, and that 9/11 was an inside job. Because of these and other extremist reflections, the House sensibly stripped Greene of several committee assignments.

Others on the “committee” included Congressmen Clay Higgins (R, Louisiana), Thomas Massie (R, Kentucky), Warren Davidson (R, Ohio), and Andy Biggs (R, Arizona). Also attending was Senator Ron Johnson (R) from my own State of Wisconsin who has been a vaccine dissembler for a while, claiming, for instance, that the vaccines have killed many people. I recently contacted the Senator’s office and asked why he believed that. They quickly responded and sent me to a web site that was very professional looking and had very many graphs and tables claiming to show that the vaccines caused hundreds of thousands of deaths. The problem is that the data they used to put said graphs and tables together were bogus. The statistics were fraudulent (for example to test the site, an MD submitted a claim saying that the vax turned him into the Incredible Hulk. His claim was accepted!). Anti-vaccine crusaders with radio and blog platforms have urged their audiences to post false information on the site, and the website itself had been debunked numerous times by the investigative press and in science journals for incorrectly reporting the data. I pointed this out to Sen. Johnson’s office and never heard back, in contrast to their earlier quick response. Go figure.

Back to the Shadow Congress Committee meeting: Three people testified: A lawyer, an obstetrician-gynecologist, and a scientist. A summary of the testimony of each, with my comments follows.  

The lawyer. Forty-six-year-old Thomas Renz, went first. He passed the Ohio bar exam in 2019 after five tries and since has made a name for himself, along with the MyPillow guy, Mike Lindell and others, as a COVID conspiracy buff. Renz made three unsupported claims enumerated below: 

  1. First, Renz declared without any evidence, that it is vaccinated people who are dying. However, a study published in the Journal of the American Medical Association showed that in 2021, unvaccinated adults were 12 times more likely to be hospitalized and in 2022, that they were 6 times more likely to die after infection. Science shows that COVID vaccines have been estimated to have saved the lives of more than 3 million Americans. Renz’s says otherwise. Who are you going to believe, science or the lawyer, Renz?
  2. The lawyer also claimed, again without proof (a lawyer without evidence?), that “COVID is not as bad as SARS or MERS but about as dangerous as a bad flu season.” Well. The first human coronavirus outbreak, SARS-1, was identified in Asia in February 2003. It infected a tad more than 8,000 people, killing ~800. By July 2003, the outbreak was contained without a vaccine. The second coronavirus outbreak, called MERS (Middle East Respiratory Syndrome), appeared in June 2012, in Saudi Arabia. That virus infected >2,500 people, killed about 900 and also was contained in a short while without a vaccine. Compare those numbers to SARS-CoV-2, which so far has killed almost 2 million people in the United States and 7 million people in the world. And four years later it continues; it is not contained even though we have several vaccines. Except for the 1918 flu pandemic, which killed more than 50 million people worldwide (that was before flu vaccines) COVID is worse than any other flu in history and much worse than SARS or MERS. Renz’s lawyerly opinion is bunk. Why is he even testifying on a medical matter?
  3. Renz saved the best for last. With the help of an “unnamed whistleblower,” Renz claimed, without proof, of course, that "something suspicious" happened in November 2014 at Fort Riley, Kansas, when the Department of Defense (DOD) and the CIA, in collaboration with the Wuhan Institute of Virology, created SARS-CoV-2 virus. Not in the Wuhan lab mind you, but in Kansas in 2014! To support his claim, Renz offered nothing! It was just his opinion. Renz also asserted that Tony Fauci, the CDC, FDA, and the DOD played a part in a massive cover-up of all this (so how in the world does HE know?). He unbelievably stated that Hunter Biden was also involved (why not?). Funny how the FBI hasn’t picked up on any of that. Renz knows because he says he does. Trust him, he’s a lawyer without evidence. But that is good enough for the Shadow Congress.

The Ob/Gyn. Next up was Kimberly Biss, MD, a well credentialed obstetrician and gynecologist practicing in Tampa Bay and St. Petersburg, Florida, which makes her testimony all-the-more-difficult to understand.

She claimed that after receiving COVID vaccines, an unspecified number of women in her practice suffered unsubstantiated menstrual cycle irregularities including severe, persistent bleeding. However, the only way to reliably determine whether COVID vaccines caused these  changes in menstruation is to compare the symptoms in women who got the vaccine to women who did not. She didn’t do this. Anecdotal observations like these offered by Biss usually don’t include both groups, which is why medical science considers anecdotes to be unreliable and instead rely on controlled clinical trials to base medical science opinions.

Furthermore, real scientific comparisons between vaccinated and unvaccinated women have been done but these were not entered into evidence at the Shadow Congress Hearing. A study of more than 1,100 women performed by the Boston School of Public Health found that there was no association between COVID-19 vaccination and cycle irregularity, bleed length, heaviness of bleed, or menstrual pain. So, which is more credible, Biss’s personal uncontrolled anecdote on an unknown number of patients whose medical history is unknown vs a controlled scientific study on over 1000 patients with carefully documented medical histories and compared to a comparable cohort of unvaccinated menstruating women?  

Biss further testified that in her practice miscarriage rates went up in vaccinated women, again without indicating the number of patients she saw and without providing any medical documentation. She again failed to note the miscarriage rates in unvaccinated women (why does she always leave out the data from unvaxed women?). Another scientific study of 40,000 pregnant women showed that vaccination was not at all associated with an increased risk of premature births. And other controlled studies have shown that COVID vaccination during pregnancy does not increase the risk of birth defects. Again, what would you believe, Biss’s anecdotes or several well controlled peer-reviewed and published science studies?

Biss continued her misleading anecdotal testimony by claiming that it was unsafe for vaccinated women to breastfeed because she "heard" it caused myocarditis in babies in Scotland. She failed to provide any substantiation for her wild claim that no one else seems to have heard. Not only has breastfeeding proven to be safe in women who have received COVID vaccines, newborn infants benefit from vaccine-induced antibodies in breast milk. This provides newborns with their initial protection against COVID as they develop their own immune system. That is a normal part of the maternal-fetal immune system that newborns immensely benefit from. That is basic immunology.  

Finally, and most outrageous was Biss’s stance on vaccinating children. She advised against vaccinating kids falsely claiming that only “three in one million children will die from COVID.” One wonders where she gets her facts like this and like those about myocarditis in breast fed babies in Scotland. As of January 2023, COVID was the leading cause of infectious disease deaths in children. Contrary to Biss’s claims, the COVID death rate for children less than one year of age was 43 per million. Hundreds of young children have died from COVID and many, many more have been hospitalized long term with the very serious condition called multisystem inflammatory syndrome, or MIS, which I have written about in these pages. COVID is much more serious than the flu for kids. None of those deaths or serious illnesses in kids are acceptable. Her claims to the contrary are simply irresponsible for a physician to make.

Finally, the scientist. Perhaps the silliest testimony in front of MTG’s “shadow” committee came from a scientist and physician named Robert Malone who recently has gone around claiming he “invented” the mRNA vaccine. He did not. In the late 1980s and early 90s, labs around the world were fixated with the idea of trying to express genes in cells via transferring DNA into cell cultures. The technique was called “transfection.” It promised to be a powerful tool for studying the function of genes in cells, but proved enormously difficult as I wrote about earlier. My own lab considered trying it, but discarded the idea in favor of another approach, viral-based gene transfer, which we often used to study gene function, and which some might call routine gain-of-function research as I also described earlier in these pages.

Meanwhile, Malone was a small part of the “transfection” bandwagon and in the late 80s published two papers showing it was possible to transfect fragile mRNA protected by a lipid micro-bubble into cells (most labs transfected DNA, which was easier to work with than mRNA). Undoubtedly, his research represented a stepping stone on the path to developing the vaccines, but he had no role in vaccine development. He was one of very many scientists who contributed incremental advances that ultimately made the vaccines possible. He is now way overselling his role. The technology that produced the mRNA COVID vaccines recently won a Nobel Prize and Malone was never mentioned in the invention. He is only a giant in his own mind.

More to the point, Malone testified that the vaccines are contaminated with fragments of DNA and dangerous. He argued, without evidence and contrary to all other science, that these DNA fragments alter cellular DNA of vaccine recipients, causing cancers, autoimmune diseases, and a variety of other disorders. For pregnant women, Malone further opined, again without a shred of proof and contrary to common science, that these DNA fragments could cross the placenta and cause birth defects. Furthermore, according to Malone, the FDA, the CIA, and other government agencies know about this DNA contamination but are covering it up (is Hunter involved in this too??). Again, he offered no evidence at all for this allegation. But, maybe we can excuse him, because there is no evidence to offer.

The idea that the vaccines are contaminated with DNA detritus is old news. All vaccines contain DNA of different sorts, which has never caused any harm as long as vaccines have been given. In fact it is biologically impossible that miniscule amounts of DNA detritus could mess up our cellular DNA. It is irresponsible, and scientifically ignorant of Malone to simply throw this out without elaborating. He didn’t elaborate because to do so would have ruined his “Frankenscience” innuendo that seemed to duly impress the scientifically naïve Shadow Congressional audience he spoke to.

The mRNA used in the vaccine is produced from a DNA strand. The DNA strand is then digested with an enzyme called DNase which chews up all DNA strands, leaving only the DNA building blocks, or remnants of it behind; DNA detritus. It is like taking a large building and demolishing it into its bricks. The large mRNA molecules are then easily biochemically separated from most of the DNA detritus. Even if there were miniscule traces of DNA detritus left over, it is biologically impossible for it to damage cellular DNA. It simply is recycled and reused by our cells. Our cells do that all the time.

But, maybe larger, intact DNA fragments could mess up our cellular DNA? We are exposed to large fragments of DNA all the time with no adverse effects. Consider the following two points: 1) we eat foreign DNA from plants and animals all the time and that DNA enters our blood stream in intact pieces much larger than the digested detritus we have been talking about. Yet, we are totally unaffected by this. 2) We also get vaccinated with whole DNA virus vaccines and have no concern that they affect our cellular DNA. Studies have shown that there is NO genotoxic effect of any of the vaccines.

Finally, consider the inherent conflict in Malone’s position. On the one hand he goes around promoting himself as the inventor of the vaccine technology. He even laments that he has not been given his due credit for the invention. Then he tries to discredit the same invention as something very dangerous and that should not be given to people because it causes enormous harm.

Which is it? Do we laud Malone as he would like for discovering a lifesaving vaccine, or pillory him for creating the dangerous vaccine he says it is? The man is as confused as his testimony.

This is what some of our Congress people spent their time doing last November. The Congressional Flake Caucus wasting their time and our money on a "hearing" without a single reputable testimony. At least it received the very little attention it deserved.

Last word. In an earlier post in these pages I asked the question if it was criminal to intentionally mislead people about lifesaving vaccines. That question is worth raising again, now.


‘Tis The Season To…..Mask Up Again??

"It's a bug hunt!"

-Private Hudson, in “Aliens”

"Influenza-like illnesses" are increasing at an alarming rate across the country. Yup, ‘tis the season for respiratory diseases and we have more than one to worry about. In years past we mostly worried only about the flu and, sometimes as an afterthought, colds, which aren’t of much concern. But in late 2019, a brand new and very weird bug appeared on the scene, SARS-CoV-2 that caused COVID. It seems that the bug and disease will be an annual guest from now on. This year, we also see a surge of a third bad bug, respiratory syncytial virus, or RSV. All these viruses cause what have been collectively labeled “flu-like illnesses” and together they seem to be worse this year than recent years. The CDC reports that hospitalizations for flu-like illnesses have been steadily rising and that the peak is still to come.

As a result, we are beginning to see increasing reports of a return to local mask mandates. In my own community of Madison, Wisconsin, two major health networks just announced their return, like a bad TV rerun. This includes the University of Wisconsin Health network, where I receive health care. Glad I kept a few masks on hand. What’s in your glove compartment?

I also have read where some grocery stores are now requiring masks. Some stores only require masks on certain days of the week so that customers can select to shop on mask-required vs mask-optional days. Some colleges and large companies reportedly also are beginning to require masks again. So far these mandates are very local and are not a national phenomenon. It is feasible that mask mandates in public spaces and especially for travel could increase if infections and hospitalizations get more serious.

As I often say in these blog posts, “we will see.”

Why is the flu and RSV, which have been around almost forever now causing more than their usual problems? A hint was presented in a blog post I published about a year-and-a-half ago, “What Happened To The Flu And Other Respiratory Diseases?”  In that apparently prescient post, I reported that the world had seen a huge reduction of all infectious respiratory diseases due to the protective non-pharmaceutical interventions (masking, sanitation, isolation, quarantines, closings, etc.) designed to physically protect people from the new coronavirus. They were so effective that some strains of other common infectious viruses are thought to have gone extinct!

That is great news! But, it also means that the world also missed its regular natural booster of common bugs and our herd immunity to them waned. Our youngest were never exposed to those bugs and the rest of us became less resistant to future exposure and that future is now. We are now paying the piper for that lapse in a “bug boost.” Hence, flu and RSV temporarily are having their way with us and enjoying it. At least they are not nearly as nasty as the coronavirus initially was and still could be with a couple of insouciant genetic tweaks.

“Influenza-like illness,” is a catch-all term coined by the CDC to corral COVID and the other two viral diseases. Together, the three have reached an epidemic point in the US and other places across much of the world. The Figure below shows that the US epidemic is currently hitting Southern States the hardest, but expect it to migrate Northward in the next few weeks.

What do the different colors in the Figure mean on a practical level? I can offer one anecdotal example. According to the map, New Jersey, while not a Southern State, still is being hit hard. A family doc wrote about a week ago that all the hospitals in his health system are at capacity. He was unable to send a patient to the preferred ER because its hospital was full due COVID, flu and RSV cases. And the patients with these flu-like respiratory infections who were filling the beds were not necessarily elderly. Most are in their 40’s-50’s. Unsurprisingly, the hospitals and clinics in his health system again require masks. Their staffing is becoming a critical issue as providers also become ill and turn into patients. This is becoming too reminiscent of the early stages of the COVID onslaught when hospitals where overwhelmed and medical personnel were dropping like flies. So far, this experience is sporadic across the US. But, it is becoming concerning.

ORI
Outpatient Respiratory Illness Activity Map Determined by Data Reported to ILINet
This system monitors visits for respiratory illness that includes fever plus a cough or sore throat, also referred to as ILI, not laboratory confirmed influenza and may capture patient visits due to other respiratory pathogens that cause similar symptoms. From the CDC.

The incidence of RSV is high. RSV hospitalizations have increased 60% nationwide over the past four weeks. A couple of deaths in children have been reported in my state. The vaccine for RSV is brand new this year and recommended for people over 65 and for kids; i.e., those at highest risk for severe disease. It definitely is worth it.

Flu is moderate right now, but expect it to soon blossom. Hospitalizations among all age groups increased by 200% for influenza in the past four weeks but still remain below Covid-19 and RSV hospitalizations. For now. They are expected to increase as the peak flu season has yet to arrive.

And then there is our relatively new friend, COVID. On a national level, COVID virus transmission is “very high.” After the post-Thanksgiving surge, as determined by monitoring viral loads in wastewater samples (“take-your-kids-to-work” days in that profession must be fun!), virus levels plateaued. But expect another sharp rise after the Christmas/New Year’s holidays. We have consistently seen this pattern in previous years.

Cov-2 is one of the most mutable viruses that the world has inflicted on us. That means we are constantly seen new variants arising. Surprise, the Omicron subvariant JN.1 is coming onto the scene. It’s the spawn of variant BA.2.86, which was discovered over the summer and was concerning because it came out of nowhere with a whopping 35 mutations in the spike protein (the more mutations, the greater the chance for another very nasty bug). While BA.2.86 caused a comparatively mild disease, it quickly mutated to JN.1 with just an additional single change in the spike protein that made it much more infectious, but it still remains fairly mild. With just one mutation, it became the fastest-spreading CoV-2 variant in the past two years. With all its changes, JN.1 is so different from its Omicron grandparent that there is considerable scientific debate about whether JN.1 should be given its own Greek letter designation, Pi. A weighty debate indeed.

But, a bigger question is whether COVID hospitalizations will follow wastewater sampling trends that show JN.1 (or Pi) viral levels surging through the world, especially in the US where vaccination rates are low. It is concerning that the UK and Singapore, which have high vaccination rates, are now seeing a steep increase in hospitalizations due to JN.1 (or Pi). So why not expect the same or even worse in the undervaxed US? Last week, the CDC warned about such a potentially huge impact due to the wretched combination of low US vax rates and the highly infectious JN.1 (or Pi) virus. As Private Hudson (aka Bill Paxton) in the movie Aliens might say, thanks to the antivaxers, “Game over, man! Game over!”

Also of new concern is that some scientists are now beginning to believe that COVID infection could be damaging our immune systems. If true, that could make infected people even more vulnerable to the other bugs out there such as flu, RSV, and others including bacteria and fungi. COVID could also cause immune dysregulation leading to new-onset autoimmune diseases. So get your COVID vaccines! They can protect you against illness beyond COVID!!

Finally, another concern is that the rapid home tests for COVID are proving to be only 30% reliable very early after infection before symptoms start. In other words, if you believe you have been exposed to COVID, but your home test comes up negative, don’t necessarily believe it. Retest yourself 24, or preferably 48 hours later or when you show symptoms like a fever, cough, etc. If that second test also is negative, you have pretty good confidence you are COVID free and have some other bug.

The pragmatic bottom line. There is a lot of coughing, sneezing and other respiratory distress going around, and it will increase in coming cold weeks as we bundle up and crowd around others indoors. To improve your odds of staying healthy, remember these things:

  • Limit your time around indoor crowds.
  • If you have indoor gatherings, crack your windows and bring out the fans to increase air circulation and air exchange with the outdoors. There is very good evidence that good ventilation really matters and that the amount of viruses we breathe in makes a big difference in terms of whether we get sick and how sick we get. It is worth a few extra dollars on the heating or electricity bill to avoid nasty illness.
  • Room air filters are also a good idea.
  • Get vaccinated!
  • Wash your hands often.
  • If you do get sick, STAY HOME! I have always hated the “brave” soul who came to work with a cough and sneeze. Don’t share your agony!!
  • And there are the good old fashioned masks for use in crowded places, especially in auditoriums, on planes, and other packed indoor situations. I don’t care what the naysayers say about masks, they are flat wrong. They don’t think twice when a store sign requires shoes and shirts to enter. So why do masks bother them so much? They WORK as I have written here before, over and over. Empirical evidence proves masks work. That is why the entire medical profession continues to use them.

Finally, as I have repeatedly admonished, please get vaccinated. Vaccine and booster uptake for all three viruses has been dismal this year. Failure to vax is a major driver in the surge of the flu-like respiratory diseases we are seeing. If you have not gotten vaccinated for all three circulating viruses, why the heck not?? It is way better to prevent disease than to treat disease. A sore arm is much less of an inconvenience than suffering the flu, RSV or lying in a specialized hospital bed turned on your stomach breathing with a ventilator because of COVID.

As I have written in these pages, having COVID can be worse than any flu you ever had. It also puts adults at risk for dealing with weeks of long COVID and getting new-onset diabetes and immune dysfunction. COVID also is much worse than the flu for many kids and puts them at risk for multi-system inflammatory syndrome (MIS).

Why risk what can be prevented by a simple vaccination?

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What We Learned From Sweden’s Response To COVID

Sometimes I wonder whether the world is being run by smart people who are putting us on or by imbeciles who really mean it.
― Laurence J. Peter, The Peter Principle

Many people have asked why we didn't let the virus hit us like a big wave and get it over with. The Great Barrington Declaration (GBD), a letter penned by three physicians, favored such an approach and called it “focused protection.” It recommended quarantining the highly vulnerable, i.e., the elderly and those with high risk factors like diabetes, heart and lung disease, etc., and letting the virus run amok through the rest of the population to quickly build natural herd immunity across the country. They said we should do away with non-pharmaceutical interventions that prevent infections, such as masks, sanitation, personal distancing, quarantines, closings, etc. The recommendation was published as a letter on October 5, 2020 because no medical journal would accept it as an article. Vaccines were still considered to be months away at that time, but actually began to roll out in mid-December of that year. Admittedly, the letter’s authors did not have a crystal ball.

We didn’t accept that recommendation, but Sweden did something very similar on their own and kept their country open and had considerably less morbidity and mortality than the US. Armchair health experts who learned their subjects at Google and Facebook Universities have been clucking their tongues and scolding the CDC and public health professionals ever since. Should we have responded like Sweden did? Would it have been better if we had followed the recommendations made in the GBD?

When the declaration came out, it was widely panned as being ridiculous by health experts and organizations around the world. A Yale epidemiologist pointed out that almost half the US population would be considered to have an underlying risk factor for COVID meaning that half the population would have to be quarantined from the other half, not much different from the protective measures already underway at that point. It also would have meant that people at less risk would be exposed to a rather nasty virus. They essentially would be sacrificed to a disease more lethal than any flu we have encountered since 1918. And then there is the problem with long COVID and other morbidities such as an uptick in new onset diabetes in many COVID survivors. Even though kids have a very low level of mortality from COVID, the disease was still much worse than any flu for them and too many of them were hospitalized in serious shape with a malady called multisystem inflammatory syndrome or MIS. This was the sacrifice the folks who proposed the GBD were willing to impose on half the population.

Anyway, this post is supposed to be about Sweden, not the US. Did Sweden’s experiment turn out as positive as many people believe? It depends on which countries you compare it to. Comparing the Swedish experience to that of the US, it seems they did pretty well. They did not shut down and had much less mortality than we did. But is that an accurate apples-to-apples comparison? Sweden is a country of just over 10 million people. Its demographic is much more homogenous than that in the US and it has much less poverty. In the US, COVID hit impoverished and minority populations especially hard. They have fewer medical resources to deal with the disease. In contrast, Sweden does not have such a large minority or poor population and it has cradle to grave social welfare for everyone, including medical care. It does not at all resemble the US.

It is more accurate to compare Sweden to its neighboring Nordic countries with similar populations, demographics, and social welfare, but that also enacted more stringent social controls in response to the pandemic like the US did.

It turns out that compared to other Nordic countries, Sweden fared quite poorly with the highest mortality rate. Sweden had four times the number of COVID deaths compared to many of its neighbors. In particular, it had ten times the COVID death rate of Norway.

What about the economy? Of course the Nordic countries that enforced public and commercial shutdowns suffered significant economic hits like the rest of the world. Importantly, so did Sweden, which kept its economy open. Nevertheless, the country suffered as much economic downturn as its neighboring countries that enforced stricter shutdowns. In fact, the Organization for Economic Cooperation and Development and Development (OECD), of which Sweden is a member, reported that the country actually did markedly worse than Denmark, Norway and Finland. It seems that economic health is not only related to open commerce, but also to the public health of the country. Sick people do not work or venture out to buy things. It seems that public health affects economic health. That was not considered in the GBD, which was concerned about the economic impact of closing down commerce via fiat. They did not consider the economic impact of closing down commerce by hospitalizing so many people.

As these effects of its open policies became clear, Sweden eventually began to enforce greater social restrictions later in the pandemic, but the damage had already been done. The architect behind its initial open policies eventually admitted that things did not work out as planned. And in December 2020, Sweden’s King Gustav publically declared that the government’s approach had failed.

The real lesson from Sweden is that if you keep things open and people get sick, the economy still suffers in a pandemic. As far as the economy goes, it is a case of “damned if you do and damned if you don’t” enforce public restrictions.

And if you don’t, people still get sick and die and dead people stop buying things.

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US Life Expectancy Finally Bounces Back Up

Game over, man! Game over!” --Bill Paxton as Private Hudson in Aliens

As I wrote in these pages a couple of years ago, the US suddenly lost a whopping 1.3 years of average life expectancy due to COVID. It had that big of an impact on the country in excess deaths. And before some moron starts saying it was due to vaccine deaths, the down turn in life expectancy, or the increase in excess deaths (i.e., deaths more than expected based on actuarial predictions) began before the vaccines rolled out and just after the virus appeared. Furthermore, the upturn in life expectancy occurred after the vaccines were delivered, as well as after the virus evolved from Delta to a less lethal variant. In the early days of COVID vaccination before vaccines were widely distributed, data showed that unvaccinated people were 11 times more likely to die from the virus than vaccinated people. At one point, 95% of hospitalizations and 99% of deaths were in unvaccinated people. The vaccines clearly prevent death, they do not cause death (unless you listen to Robert F. Kennedy, Jr. or Marjorie Taylor Greene, more on her later).

The graph below shows the dramatic drop in life expectancy beginning in 2019 and reversing about 2021. If vaccines were killing rather than saving people, you would think the curve would continue downward.

Blog pic

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Vaccines: When the Experts Lie But Claim They Are Right

Adapted from Putting Floridians at Risk, a blog post by infectious disease physician and FDA advisor, Paul Offit, MD.

The lie: In October, the Surgeon General of Florida, Dr. Joseph Ladapo, issued a “Provider Alert”, which recommended that the new COVID booster only be given to everyone over 65. This was contrary to the CDC recommendation, which recommends boosting everyone over 6 months of age. Governor Ron DeSantis agreed with Ladapo, amazingly weighing in with this: “Once again, Florida is the first state in the nation to stand up and provide guidance based on “truth,” not Washington edicts.” I guess edicts from Washington automatically are not truth, but those from the Florida Surgeon General, for some reason are, because DeSantis says so. Why does he believe he knows more than the CDC?

Ladapo amazingly claimed that the COVID boosters don’t work. He too seems to know more than the CDC! To back up this spurious claim he cited a study of 2.2 million people from Qatar who got the booster.

Backstory: At first, the vaccines were hoped to prevent spread of the Cov-2 virus as many vaccines do. Early on they did that. But it soon became apparent that vaccine protection waned faster than expected and the virus mutated faster than expected. That combination meant that the vaccines became less effective at preventing virus spread. They still retard infection early after vaccination, but that protection is quickly lost. What they do well is prevent severe illness and death. That is well documented after  a few years of experience with the vaccines and the pandemic. Therefore, the goal of COVID vaccines is to prevent severe disease—to keep people out of the hospital, out of the intensive care unit, and out of the morgue. The Qatar study showed that the booster does exactly that. Protective efficacy against severe disease was about 75 percent. Pretty good.

Back to the lie: Ladapo unprofessionally ignored this main point of the Qatar study—that the vaccine was highly effective at preventing severe disease—and chose to focus on smaller, less significant, less clinically relevant data that minor infections were not affected by the booster. On this selective date editing, he claimed the booster was entirely ineffective. He either ignorantly interpreted the study or did so dishonestly.

Ladapo also falsely claimed that the COVID boosters are unsafe, stating that, “mRNA COVID-19 vaccines present a risk of subclinical and clinical myocarditis and other cardiovascular conditions among otherwise healthy individuals.” This is an oft cited, unsupportable falsehood. The truth is that very mild myocarditis occurs in about 1 in 100,000 mRNA vaccine recipients.  In contrast, myocarditis occurs in roughly 1 in 5,000 CoV-2 infected patients. Also, myocarditis following vaccination is short-lived and quickly resolves on its own, while myocarditis caused by the virus is more serious often requiring medical intervention. Therefore, regarding myocarditis, the benefits of mRNA vaccination far outweigh the risks. Ladapo is being disingenuous citing this is a vaccine danger. And if Ladapo believes that the COVID boosters are ineffective and unsafe, as he claimed, he is, therefore, irresponsible in recommending them for everyone over 65. That would be malpractice.

In the name of standing up to “Washington edicts” and recommending people not be boosted, DeSantis is following unethical medical advice and putting Floridians at unnecessary risk for preventable serious disease. And he wants to be president. If that were to happen, we would then have real complaints about Washington vaccine edicts.

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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.

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