Coronavirus news & views

COVID: Don’t Touch My Junk

"It's not hard, (it's not hard)"

–from the song, Piano, by Ariana Grande

 

COVID is very strange. Earlier I reported that the SARS-CoV-2 virus, which causes COVID-19, a mostly respiratory disease, also messes with one’s gut health. Elsewhere in these pages, I have also discussed the relationship between COVID and new-onset diabetes type 1, Parkinson’s disease, cancer, dementia, and cardiovascular problems. That is quite a panoply of symptoms unrelated to respiratory disease. We now can also add to that complex array of health problems caused by a respiratory virus, broad effects on the male reproductive system. Ouch!!

Several reports (here, here and here) together report that COVID-infected men often complain of the following several symptoms related to male genitalia:

• Testicular pain
• Erectile dysfunction (ED)
• Reduced sperm count
• Decreased fertility
• Smaller penis size
• Decreased sexual drive
• Swelling
• Prolonged erection

How in the world does a respiratory virus affect all this in the male reproductive system to cause what is sometimes referred to as “COVID penis?” 

Well, we now know that the organs of the male reproductive system, including the prostate, testicles, and penis actually can be infected by the COVID virus and, thus, have their functions compromised. This can lead to erectile dysfunction, decreased testosterone, and reduced sperm levels in 60-75% of infected patients (see here, here)

The fact that a respiratory virus can widely infect men’s junk recently was shown by research from Northwestern University. The study used body scanning technology to surprisingly show that the CoV-2 virus had infiltrated the entire male genital tract of infected monkeys (including the prostate, persimmons, and tallywhacker). From these results, the investigators concluded that the manifold reproductive problems linked to COVID-19 are not secondary effects of fever or inflammation but rather a direct result of the virus infecting cells throughout the male reproductive system. It is believed that CoV-2 infection of reproductive tissues can make the organ’s small blood vessel linings not function properly, which then causes reduced blood supply leading to ED, maybe shrinkage, and the other consequences.

Medical researchers at the University of Florida Health found that men with COVID-19 were more than three times more likely to be diagnosed with erectile dysfunction than those who didn’t have COVID.

A July 2024 review of 16 articles involving 1250 men with active or recent COVID infection  and 1232 healthy controls confirmed that sperm count and motility are significantly reduced in infected men. The results also showed reduced testosterone levels and abnormalities in other hormones affecting sexual function. The fact that COVID has such broad effects on the male reproductive system raises a concern that the disease could be sexually transmitted. Fortunately, no COVID mRNA was found in the semen of any of the infected men, which suggests a low possibility of sexual transmission of the virus.

Another question all of this raises is how long do these effects on men’s reproductive health last. The good news is that two studies published in 2023 and 2024 showed that the reduction in sperm count caused by COVID was transient. Sperm returned to normal levels and motility 3-6 months after infection. How long other problems persist is less  at this time.

All of this information provides yet another good reason to make every effort to stay current with the COVID vaccinations.

It is not hard.

SARS-CoV-2, A Respiratory Virus That Messes With Your Gut

The CoV-2 virus that causes COVID is a respiratory bug, right? They say we catch it, not from surfaces or food, like we do norovirus, but from airborne exposure—we breathe it in. That of course, means that it causes respiratory problems. Makes sense, right? Well, Sarah Carter, 36, from San Mateo, CA, caught the virus in late 2023. Her main symptom was not respiratory but relentless diarrhea that became so sever she had to take an ambulance to the ER. The runs caused her to become dehydrated, which in turn caused a spike in her blood pressure and heart rate. She urgently needed IV fluids to treat it all. After three more days of diarrhea she finally felt better. But, six months later the GI symptoms reappeared overnight without her being infected again. Nearly everything she ate set off diarrhea. She also had bloating and pain so severe that she said it felt like acid was running through her intestines. A gastroenterologist eventually diagnosed her with post-infectious irritable bowel syndrome (IBS).

What in the world is a respiratory virus doing messing with her entrails, especially months after being infected? Did it make a wrong turn somewhere?

We have gotten accustomed to testing for COVID when we feel crummy and run a temperature, have a sore throat, runny nose, loss of smell, cough, etc.—all symptoms of respiratory infection. But Dr Rohit Jain, an internal medicine doc at PennState Health told Time that when someone complains of problems affecting the exit at the other exit of the body: i.e., nausea, diarrhea, vomiting, etc., he always tests for COVID. Another doctor, Mark Rudd, chief of infectious diseases at the U of Nebraska Medical Center also weighed in saying that, “COVID-19 is really a GI-tract disease.”

What??

If it “really is a GI disease” why are we wearing masks, distancing, and worried about respiratory infection rather than hand washing and sanitizers??

The SARS-CoV-2 virus and its disease, COVID, are very strange and threw the medical establishment for a loop after they first appeared on the scene at the end of 2019, and after COVID became a world-wide pandemic in early 2020. Docs dealt with myriad, seemingly unrelated symptoms in different patients; symptoms such as brain fog, loss of smell, severe pneumonia, hemorrhage issues that led to black toes and lungs that looked like they had filled with chocolate pudding, among many others; all from the same virus. Now add to that befuddling mix, GI problems to what was believed a respiratory virus,and COVID presents a conundrum. Docs have to now factor in the fact that many people experience no, or only mild gastrointestinal symptoms, while other patients experience significant digestive problems that can distract from the pulmonary problems which complicate diagnoses.

As we have learned more about COVID over the last few years, it has become clear that infection symptoms can also include loss of appetite, nausea, vomiting, diarrhea, and stomach pain, according to Jain’s research. A 2023 study published in Nature Communications reported that 36% of COVID patients are likely to develop GI disorders such as ulcers, pancreatitis, IBS, and acid reflux. Another recent study in Clinical Gastroenterology and Hepatology found that 40% of adults hospitalized with COVID, had at least one GI relapse a year or more later. While both of these were small studies, they are in close agreement regarding the incidence of COVID GI problems. And like other symptoms of long COVID, the GI problems can last many weeks. That is quite concerning. Weeks of diarrhea, for example, is much more than an immense inconvenience and major mess, it is a serious medical issue. But not all patients experience these symptoms, just like not all patients lose their sense of smell, had black toes, or developed long COVID. Try to diagnose and understand COVID with this range of variable symptoms! How confusing.

How can the same virus cause runs from both ends of the body; the nose and the other end?  Among the things we have learned over the last few years is that the CoV-2 virus infects cells that express the ACE-2 protein. While ACE-2 normally is important for certain cell functions, the virus decided to use it as a receptor on which to grab onto and then enter cells. The protein is found on many different types of cells throughout the body, but it is expressed in especially high levels in the lungs, which helps explain COVID’s respiratory symptoms. It turns out that ACE-2 is also highly expressed in cells of the GI tract. That explains the intestinal complications. Also, because it is found in the GI tract that could possibly make feces from infected animals, like bats, a great way to widely spread the virus to other animals, just like migrating birds spread the avian flu virus to poultry flocks and dairy herds. In fact, in 2012, six Chinese mine workers removing guano in a bat-filled cave where flying flittermice were found with COVID, developed severe respiratory symptoms. Three of them died. COVID infection from contaminated bat guano is suspected because the Wuhan lab eventually found evidence of an unknown coronavirus in the patient samples. But, this was years before the CoV-2 virus had been discovered, so the CoV-2 link to their disease comes with some uncertainty. Maybe the virus in ca-ca could be a way to spread it between people too, like norovirus is spread. To my knowledge, human-to-human spread this way has not been shown, but it makes sense to this scientist that it could. After all, since the virus is found in feces, wastewater surveillance has proven to a useful tool for tracking CoV-2 spread among human populations. It is routinely found in poop, and there is a good possibility that the Chinese workers caught it from the bat scat they were shoveling. Together, that makes it very likely that humans can spread it to other people via unsanitary practices. But, at this time, that is just the opinion of your sometimes humble correspondent. We will see.

We also now know that the virus can hide in the nooks and crannies of the  bowel for months, or even years, according to Ziyad Al-Aly, MD, an epidemiologist at the Washington University School of Medicine in St. Louis, who co-authored the Nature Communications study on chronic post-COVID GI symptoms that was cited above. This might explain why gut-related symptoms can long outlast the initial acute infection. But other possibilities to explain long-COVID GI problems continue to be investigated. This is another “we shall see” issue.

We also know that the virus can cause widespread and sometimes long-lasting inflammation, potentially affecting various organs throughout the body including the gut. GI inflammation can affect the gut microbiome, which is the collection of microbes that normally live in the GI tract and that are good for us. We have long known that changes in the gut microbiome can have manifold health effects affecting GI health, and even the well-being of the heart, kidneys and brain, including Alzheimer’s disease, which is a possible complication of COVID. Disruption of the GI microbiome also is related to obesity and diabetes and it is notable that COVID disease also is associated with new-onset diabetes. Inflammation in the gut can also damage the lining of the intestines, making them “leaky” so that nutritional goodies from foods you normally would absorb across your gut into the blood stream, instead escape into the abdomen, causing immune cells to mount an allergy-like response to foods. COVID-induced inflammation can also chew away at the nerves that control normal gut contractions (peristalsis) that move food along, and interfere with neurological signals in the gut causing pain. Not fun, ask Sarah Carter!

Since the start of the pandemic in early 2020, GI docs have noticed an uptick in IBS in COVID patients. Medical scientists have long known that other gastrointestinal infections, like those from norovirus, giardia (a parasite), or salmonella (bacteria), can lead to IBS as well as functional dyspepsia, a type of chronic indigestion that causes frequent feelings of fullness and stomach pain or burning, like acid running through your innards. Does that sound familiar? Now we can add the respiratory virus, CoV-2, to the list of infectious agents that can cause IBS and other digestive problems.

Bottom line: So, gut problems are added to the manifold issues associated with COVID disease. CoV-2 is a nasty bug that you don’t want to catch. Get vaccinated and spare yourself all these problems!

Over 400 Studies Show Face Masks Protect Against Respiratory Infection

“Sometimes we need education in the obvious more than investigation of the obscure.”

–Oliver Wendell Holmes

In my meanderings across the blogosphere, opinion pages, talk radio, Facebook, and even chatting with friends and acquaintances, I continually encounter folks who assert that masking is ineffective for protection against respiratory infections. Of course they never provide evidence to support their claim beyond their confidence that they are correct. I often reply that they should invite their next surgeon to remove his mask during the operation. I have published in these pages a few articles showing how controlled trials and real-life empirical data show this to be wrong (see here, here and here).

Now a new meta-analysis by University of Oxford researchers, or an analysis of some 400 published studies on facemasks, further confirms that if they are correctly and consistently worn masks effectively protect against respiratory infections, including COVID. The study also concludes that mask mandates are effective in reducing community transmission of respiratory pathogens. Note that health mandates have long passed Constitutional muster as I reported earlier. This new analysis was triggered by the controversial 2023 Cochrane review of non-pharmaceutical interventions for COVID, which several publications reported showed that masks were ineffective. However, Cochrane’s editor-in-chief later stated publicly that the review did not support such a conclusion and issued an apology for the confusion and a clarification. Several scholars also questioned the review’s methods and found flaws in its meta-analysis and criticized it for omitting a vast body of non-trial evidence. Hence the Oxford study was undertaken to learn the truth about the efficacy of face masks.

Face masks, along with other non-pharmaceutical measures, such as social isolation, have long been used during infectious epidemics, especially when vaccines and antibiotics were not available. This goes back to the European bubonic plague in 1619, the Great Manchurian plague (1910), the 1918 Spanish flu, etc. When there is no vaccine or therapeutic intervention to treat an infectious disease, physical isolation measures, such as social distancing, quarantine, and masks are critical.

The Oxford study. The study examined the relevant literature in a wide range of disciplines (public health, epidemiology, infectious diseases, biosecurity, fluid dynamics, materials science, modeling, data science, clinical trials, sociology, anthropology, psychology, and occupational hygiene). This included numerous randomly controlled trials as well as observational, or “real-world,” evidence. The results convincingly showed that cloth face coverings and disposable medical masks that are handed out at your doctor’s office can reduce infection risk, but the N95 respirators are much better.

In the early COVID-19 pandemic, when randomly controlled trials of masks had not yet been done, the study’s authors found a systematic review and meta-analysis of observational studies reporting that respirators and masks decreased infection risk up to 85%. Further, in a school-based cohort study, the risk of COVID among the family members of students was reduced by 30% to 40% when teachers used masks.

Other case-control and cohort studies in healthcare workers provided additional evidence of substantial reductions in COVID-19 risk associated with use of respirators. In 2020, one study found over 400-times lower odds of occupational acquisition of COVID among hospital staff using N95 respirators in respiratory, intensive care, and infectious diseases departments compared to those from other departments without continuous masking.

While cloth face masks were proven to protect against airborne infection, N95 or FFP2 face-fitting respirators were most effective. The latter fit more closely to the face minimizing ambient air from leaking through the edges. They also work differently from cloth masks, which use multiple layers as a barrier to block pathogens. In contrast, respirators pass air through a specially designed filter that uses electrostatic charges to trap airborne particles, whether dust or bugs.

The pore size in typical surgical masks and respirators is larger than many viruses, like Cov-2, but, viruses do not float around the air on their own. They are carried as passengers via respiratory aerosols, which are blocked by masks. Note that the International Standards Organization (ISO) provides standards for optimum filtration for respirators. This includes lab testing for filtration efficiency. This also includes personal testing while exercising in the face of a challenge contaminant. A respirator is considered to meet requirements when it achieves a 100-fold reduction in the challenge contaminate penetrating the barrier. Respirators outperform surgical masks by 8-12-fold. These results were further confirmed with animal Cov-2 infection experiments. Infected hamsters were separated from uninfected ones by a partition make of surgical mask material, which reduced Cov-2 transmission by 75%.

Besides lab studies and randomly controlled trials of face mask use, the authors also conducted a systematic review of 44 observational studies involving SARS-1, MERS, and SARS-Cov-2. They concluded that masks and respirators reduced the risk of infection by 85%. Overall, respirators were 96% effective while surgical masks were 67% effective. This protection was “dose dependent,” meaning that protection increased with the frequency of use of masks. Masks were not only found to protect the wearer, but also were effective and preventing infection of non-mask wearers surrounding the masked person. But, the greatest protection was when both parties were masked.

In addition, the study examined the effects of mask mandates in several different settings. The first such analysis found a progressive decline in epidemic growth rates after mandates were enacted when compared to time frames immediately before the mandates. Also, masking was an effective predictor of lower infection rates in the US. An analysis of masking in Boston schools, found a surge in CoV-2 infections after February 2022, when mandates were lifted. Similar evidence demonstrating the efficacy of mask mandates was reported in many other studies. Importantly, the meta-analysis did not find any evidence for significant harm to the health of mask wearers even during strenuous exercise. Specifically, they do not increase the carbon dioxide content of inhaled air. The biggest impediment to using them was discomfort and communication difficulty for deaf people who are unable to read the lips of a mask wearer.

Study conclusions. The claim that masks do not reduce transmission of airborne pathogens is incorrect. They work. Furthermore, the level of protection increases as adherence to masking increases. Masks are a critical part of infection control during a respiratory infection epidemic.

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.

SpaceX AND BioX Do It Again!!

“In science one tries to tell people, in such a way as to be understood by everyone, something that no one ever knew before. But in poetry, it's the exact opposite.

--Paul Dirac (1902-1984)

                                                                 

Backstory: Yup. SpaceX did it again. They landed a rocket booster on a bullseye; even catching it in the air with large mechanical arms they called “chopsticks.” The Brewers would love to have an outfielder like that!

BioX also did it again, following its last year’s Nobel Prize win for the mRNA technology that led to the very effective COVID vaccines. Just a few days before the SpaceX catch, it was announced that BioX won the 2024 Nobel Prize for using a computer, or artificial intelligence, to decipher the structure of ALL known proteins, and for using similar technology to create whole new functional proteins that promise to remediate environmental contamination and treat diseases. We are in a new brave world of science.

For those new to these pages, “BioX” is what I earlier dubbed the new, post-molecular biology (mobio) science that has been absolutely amazing. And I speak as a molecular biologist who now feels like a scientific dinosaur. What we learned from the old-school mobio is now being fed into computers which do all the work for us. Much tedious lab work has now become obsolete, which means that we are learning about our bio-world at an unbelievable pace. It also means that we are translating all that information into useful tools, such as better vaccines and medicines, and into making new proteins that do what we wish—like digest plastics contaminating our environment.

The science of molecular biology began in the 1920s with really basic questions. Swedish chemist and Nobel Prize winner, Theodor Svedberg, developed the ultracentrifuge in 1924, which was then used to determine the size of biomolecules—the first major question in molecular biology. The centrifuges were also used to separate different cell components, which played a huge role in discovering how cells function. The ultracentrifuge was a major tool used by only a few of the most advanced labs at that time. Now, pretty much every bioscience department has at least one ultracentrifuge.

Three decades after the advent of ultracentrifuges, Jim Watson, an American, and Francis Collins, a Brit, at Cambridge University, reported on their seminal discovery of the structure of DNA, which unleashed a storm of research into how it functions and deciphering the genetic code. That in turn led to much research into the other nucleic acid molecules found in cells, RNA. And that guided research into the structure and function of proteins, the things that make cells function. All that mobio research led to many, many Nobel Prizes. All that information provides the basis for the new post-mobio science of BioX.

Current story: All this background is mentioned in order to introduce the latest Nobel Prize for Chemistry, announced October 8. Three BioX chemists share the award. Demis Hassabis and John Jumper of Google DeepMind used AI to decipher the structure of millions of proteins. David Baker of the University of Washington used similar computer software to invent new proteins. It is possible that none of them ever purified DNA from a cell culture, sequenced DNA, cloned a gene, inserted a gene into cells to determine its function, etc. All of that is mobio—old stuff. These post-mobio scientists showed us we really do not need to that anymore if you can use a computer. Boy, does that make me feel old.

It used to take decades and many thousands of dollars of high tech equipment and an army of lab techs, students and post-docs to learn how a single protein, like hemoglobin, was structured and functioned. Now it takes minutes and a lap top. Computers can be used to predict the structure of any protein in the human body, which can inform researchers how other molecules will bind or physically attach to it. This is the new path for drug discovery.

These are the 2024 BioX Nobel Prize winners:

Demis Hassabis was born in London, where his parents—one a Greek Cypriot, the other Singaporean—ran a toy store. At one time, he was the second-highest-ranked chess player under 14 in the world. He began designing video games professionally before attending college. After completing a computer science degree at the University of Cambridge, he founded a video game company then returned to academia for a PhD in neuroscience. He and a fellow academic, Shane Legg, and a childhood friend, Mustafa Suleyman, founded an AI start-up called DeepMind in 2010. About four years later, Google acquired it for $650 million.

DeepMind’s goal was to build an artificial machine that can do anything the human brain can do. It also explored other technologies that could solve particular scientific problems. One of those technologies was AlphaFold, the program used to solve the structure of millions of proteins and for which the Nobel Prize was awarded. AlphaFold is built using a mathematical system called a neural network. With neural networks, computers can analyze vast amounts of data to learn to perform many tasks that were once beyond their capacity.

John Jumper, the youngest chemistry laureate in over 70 years, was born in the United States. After finishing an undergraduate degree at Vanderbilt University and a master’s degree at the University of Cambridge, he earned a Ph.D. degree in theoretical chemistry at the University of Chicago.

He joined Hassabis at DeepMind as a researcher in 2017 after Google had acquired the technology. He soon began work on AlphaFold. In 2020, Google researchers unveiled an update of the AlphaFold technology and showed that it had fully cracked the problem of predicting shapes of proteins with an accuracy that rivaled physical experiments and made lab rats like me obsolete. Sigh....

With AlphaFold, the Google team was able to calculate the structure of all human proteins, and then, according to the Nobel committee, it deciphered “the structure of virtually all the 200 million proteins that researchers have so far discovered when mapping Earth’s organisms.” Holy moly!!

David Baker’s work preceded the emergence of these AI models and focused on creating novel proteins. A Seattle native, Baker earned his undergraduate degree from Harvard in 1984 and in 1989, a biochemistry PhD from the University of California, Berkeley. He now serves as the director of the Institute for Protein Design and is a professor of biochemistry at the University of Washington (the other UW). In 2003, Baker and his colleagues created the first entirely new protein: a molecule called Top7. The molecule was useless but symbolic.

Since then, the researchers have used a computer model called Rosetta, which searches databases of existing proteins to find a sequence that might create a desired structure. Baker realized that if he could create a novel protein structure, he should also be able to create proteins “that actually do things,” like break up the amyloid fibrils that are thought to cause Alzheimer’s disease. Or digest plastic bottles. Or oil contamination from spills.

So far, his lab’s novel proteins—created with a more advanced iteration of Rosetta—have already been the basis of several potential medical treatments, like an antiviral nasal spray for Covid-19 (on which I will soon blog) and a medication for celiac disease. A Covid-19 vaccine, SKYCovione, based on his one of his lab’s proteins, was approved for use in South Korea in 2022.

Baker is also a co-founder of more than 20 biotechnology companies.

Congratulations, BioX! Stay tuned, more is sure to come.

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.

Still Digging Into Long COVID

It is the glory of God to conceal a matter; to search out a matter is the glory of kings.

            --Solomon

…such is the mystery of long COVID; a malady with many symptoms and no simple diagnosis—not a blood test, not even an easily agreed upon constellation of symptoms to define the malady. Yet it has a  single name, Long COVID. A simple name for a hodge-podge of unrelated health problems for which patients very often complain to their docs who very often wave off as malingering, or “in your mind”, or simply by shrugging. It is the lucky long COVID patient who presents with specific symptoms that their physician can write in Latin in their chart.

COVID itself began as a mysterious disease—THAT is one of the biggest understatements of recent memory! Long COVID has proven an even greater mystery. We have gotten a good handle on COVID itself, but still struggle to understand what long COVID is all about, what causes it (probably many different things, depending on the person), who will get it and why, who will not get and why not, how long will it last, can it be prevented, how do we accurately identify it, how can we treat it once we identify it, and so on? Medical science struggles to answer these questions.

Yet, some progress is being made; probably not fast enough if you are a long COVID sufferer, but medical science often moves at a glacial pace. Here, I describe some of our recent advances in learning about the problem.

Earlier, as the pandemic was fulminating and the health community was frantically trying to wrap its head around weird things like black toes, lungs filled with what looked like chocolate pudding,  loss of smell, etc, etc, people were other getting odd symptoms that were not resolving even after they cleared the virus: brain fog, fatigue, chronic cardiovascular problems, hard-to-describe general malaise, and other unconnected symptoms that lingered like a bellhop waiting for tip. At a loss for specific diagnosis, the maladies were deemed, long COVID.

I earlier wrote about this mystery malady and speculated on the high incidence of the illness around the world. Extrapolating the numbers, I predicted it could have a huge impact on world health and economics in coming years. I was right according to a new study reported in the prestigious journal, Nature. About 400 million people in the world (or 6% of the world’s population) have had long COVID since the pandemic began. About 13.7 million people in the US currently have long COVID. The study cited other studies suggesting that only 7 percent to 10 percent of long Covid patients fully recovered two years after developing long Covid. They added that “some manifestations of long Covid, including heart disease, diabetes, myalgic encephalomyelitis and dysautonomia (a dysfunction of the autonomic nervous system that can affect the heart, bladder, intestines, sweat glands, pupils) are chronic conditions that last a lifetime.” A lifetime of long COVID?! How to treat long COVID remains very elusive because of its plethora of unrelated health problems.

Long COVID unsurprisingly has a huge financial cost as well. It costs the global economy about $1 trillion each and every year! This includes direct health costs incurred by patients with long COVID, but also the cost of their not being able to work. This expense will continue as long as long COVID remains, which, in turn, will continue as long as we have COVID.

While our inability to effectively deal with long COVID remains an elusive goal, there is some good news. The rate of long COVID cases has sharply declined with the appearance of the vaccines according to a large new study. It appears that vaccination prevents long COVID by preventing severe illness. Unfortunately, vaccines do not eliminate all the risk of long COVID since even some people with mild illness can develop long-term complications. This study was based on an examination of medical record data from about 450,000 VA patients who had contracted COVID between March 1, 2020 and the end of January 2022. About 3.5% of vaccinated people in the database had long COVID, compared to about 7.8% of unvaccinated people. The rates of long COVID also varied with the strain of virus contracted. The Delta version, which produced more serious disease also produced more long COVID cases than did Omicron, which caused milder COVID.

And the beat goes on. Will we ever get a handle on long COVID so it can be better prevented, diagnosed, and treated?

We will see, won’t we?

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.

NIH Launches First Trial Of Nasal COVID Vaccine

"Taking a new step, uttering a new word, is what people fear most.”
― Fyodor Dostoevsky, Crime and Punishment

Earlier in these pages I described how the mucosal immune system is different from the general immune system of the body. Your mucosa (i.e., the lining of your nose, mouth, throat, sinuses, lungs, etc.) has its own robust immune defense and produces different types of antibodies in response to invaders. The nose, mouth and throat are often the first line of defense to airborne pathogens, such as the flu and SARS-CoV-2 viruses. So, when you are infected via the mucosa by an airborne pathogen, it activates a local immune response while eventually sounding an immune alarm for the body-whole. But by the time the infection settles in and the rest of your body responds, it is all-out immunological warfare and you feel crappy (hope I am not being to technical). Sometimes the bug wins too. Too often, especially before we had the vaccines, COVID won, and folks were hospitalized in dire straits with tubes attached to machines keeping them alive, too often failing.

The amazing vaccines we developed in record time were delivered into an arm muscle to stimulate our general body immune response, not our mucosal immunity. This meant that even though we had immunity, the virus could still enter us, set up shop and wait until the general body immune reinforcements arrived. Those reinforcements were quite effective at preventing serious disease, but you still would get ill.

Wouldn’t it be nice if a vaccine could be developed to nip the infection in the bud at the site of entry--in the mucosa--so it could not set up shop at all? That is an idea that has been percolating in the minds of immunologists for a while. It is the idea behind a mucosal vaccine that I described earlier.

But, if it is such a good idea for the CoV-2 coronavirus, why not for flu or other airborne pathogens that have been around much longer? Indeed efforts to develop nasal vaccines for influenza have been ongoing for a couple of decades. But, when is the last time you got a nasal spray vaccine for the flu? The track record has been mixed. The FluMist nasal flu vaccine was approved for kids in 2003. Initially it was a convenient alternative to the injected vaccine. But, it showed limited efficacy in adults. Early on it was deemed just as effective as the standard vaccine in kids, not better as hoped. More recently it was reported to not be so effective. As a result it is no longer recommended by the American Academy of Pediatrics. It clearly did not rise to the hope we had for a nasal flu vaccine.

All the above negativity for the early nasal flu vax doesn’t mean that the idea of a nasal flu vaccine is invalid. Researchers will test different sorts of flu antigens for the nasal approach. FluMist used a live, but attenuated virus in its nasal vaccine. That means kids snorted a live virus that could infect cells but not cause disease. Perhaps a different flu antigen would be more effective? But, frankly, it is hard to get more realistic than a live-attenuated virus.

Nevertheless, another promising new flu nasal vaccine candidate is FluGen’s, M2SR, developed by researchers at the University of Wisconsin-Madison. This vaccine is a bit different because it uses a wholly live virus with an essential replication gene deleted from its DNA. This means the virus is fully functional except it can’t replicate and cause illness. That makes it a little different from the live-attenuated virus. It should stimulate the immune system like a natural infection, but begs the question: how will that be different from the immune response generated from a live attenuated virus? How will that crippled snuffed virus stimulate a different immune protection from the sniffled FluMist attenuated virus? We will see, won’t we? That is why we do such experiments.

Back to COVID. This summer, NIH launched the initial Phase 1 trial to begin testing such a nasal COVID vaccine.

The vaccine. The vaccine is a mouse virus (MPV) in which a piece of the CoV-2 spike protein is expressed. MPV does not cause human disease but does like to stick to human and primate mucosal epithelial cells and should be an effective vector for delivering the spike protein sequence where it can tickle an appropriate immune irritation. In animal studies, the experimental virus was safe and produced a robust immune response in the mucosa lining the nose and respiratory tract of experimental animals. All very encouraging, hence the move to human trials.

The human trial. This is a Phase 1 trial, the first step of any experimentation in humans. Phase 1 trials do not look for efficacy and are done on quite a small number of patients, anywhere from 20-100 subjects who are not tested at all for resistance to the disease. The purpose simply is to look for common safety issues like whether the vaccine causes a general adverse reaction with increasing doses and how well it induces an immune response (i.e., anti-spike protein antibodies) at different doses. Using this information, a Phase 2 study can be designed including more subjects, usually hundreds. This begins to look for more subtle side effects and is the first test of the ability of the vaccine to protect against COVID disease. This would be a controlled trial where experimental vaccine recipients are compared to a control cohort who do not get the nasal vaccine, but probably a placebo. If data collected from this study warrant, then a Phase 3 study is done on thousands of patients to further refine the safety and efficacy profile of the vaccine.

The Phase 1 study that is underway is being led by the National Institute of Allergy and Infectious Diseases and is enrolling 60 subjects at trial sites, which include the Baylor College of Medicine, Houston; The Hope Clinic at Emory University in Atlanta; and New York University on Long Island. The immune responses of volunteers will be followed for one year. So, it will be a while before investigators have the data to begin Phase 2 trials.

Bottom line. This is just the beginning and it will take several years to finish. If successful, this would represent the next generation of COVID vaccine. Finally, as I have often ended my blog posts…

…we will see.

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.

Coronaviruses, Colds And COVID: And Cool Immunology

“The most exciting phrase to hear in science…is not ‘Eureka!’ but ‘That’s funny…’”

–Issac Asimov

 

Background. Your run-of-the-mill common cold virus is sometimes related to its more infamous relative that caused the world all sorts of consternation between 2020-2023, and still demands respect like an aging rock star who might still have some chops left. I, of course, allude to SARS-CoV-2.

Yup, the now infamous family of deadly human coronaviruses, which includes the original bat-borne SARS-CoV-1 (which caused the first SARS pandemic in late 2002), its Middle-Eastern camel-riding cousin (that caused MERS in June 2012), and the recent, much more traveled, durable, and concerning SARS-CoV-2 (origins so far unknown and the cause of COVID-19), have some lesser known, ne’er-do-well cousins that have long traveled among us. I refer to certain viruses that visit us often and are as unwelcome as a distant cousin who arrives unannounced needing a place to crash for a few days. This is the “common cold virus” which actually is several different kinds of viruses. Cold viruses are all as irritating and inconvenient as said uninvited distant cousin, and about as enjoyable as a hangover; but seriously debilitating or life threatening? They are not.

The common cold is mostly caused by one of three families of viruses; rhinovirus (not related to any large mammal), adenovirus, or a coronavirus. Yup, a distant cousin to that bug that caused so much serious illness and death across this blue orb during the COVID pandemic also is one of the causes of the mostly benign, but very annoying common cold. In fact, there are four different types of coronavirus cousins that cause 15-30% of the “common colds” in adults. Isn’t it interesting that one coronavirus, like SARS-CoV-2, can kill you, but its cousins just make you sneeze and your nose run like a leaky faucet, but that is all. Aren’t viruses fascinating?

Facts. Just as between unwelcome distant cousins, there are genetic similarities between the dangerous CoV-2 and its nettlesome coronavirus kin that just cause colds. And recent studies found that infection with one of these coronavirus cousins can indeed confer some immune protection to the other distant cousins. In other words, if you were infected with CoV-2, you likely had a much milder cold, if you caught one at all. And vice versa! But the funny thing is that vaccination against COVID did not also protect you against a cold like an infection would. What??

This stuff makes viral immunology so much fun.

To confirm all this, one study showed that this cross protection only occurred in people who had a definite bout of COVID caused by the coronavirus, and the reduced incidence of colds only occurred for colds also caused by a coronavirus, and not for a cold caused by unrelated rhino or adenoviruses. Clearly prior exposure to a different member of the coronavirus family conferred some immunity to other members of that family, even to distant cousins. Also, just being vaccinated to the CoV-2 spike protein did not confer this sort of protection to future coronavirus-caused colds. Wow! This kind of discrimination and specificity gets immunologists salivating like a Pavlovian dog to a ringing bell. I know—I am wiping secretions off my keyboard as I type.

Vaccines to just the spike protein quickly generates antibodies that neutralize the virus and thus prevent serious disease. But, that only offers short term protection to just that coronavirus from whence the spike protein sequence came. The viruses quickly mutate their spike surface proteins so the viral cousins cannot be recognized by the spike protein alone. That is why anti-spike immunity and the vaccines are not very good at protecting against re-infection for very long and why the vaccines don’t confer immunity to distant coronavirus cousins.

However, the immune system is a multi-layered security system. Besides these short-lived neutralizing antibodies that target the coronavirus spike protein (or similar surface proteins in other viruses), other layers of the immune security system can also be generated to other molecules across the SARS-CoV-2 genome following infection with the whole virus (see here and here). These other genome sequences are often more conserved and less likely to change between distant coronavirus cousins, than the highly variable spike protein sequence. This means that any immune response generated to one of these more boring, unchangable sites on a given coronavirus, can also recognize similar sequences on distant cousin coronaviruses.

But who, other than an immunology nerd really cares if having COVID protects you against a future cold? What about the reverse? Can having a cold caused by a coronavirus cousin generate some protective immunity to the nastier SARS-CoV-2 and protection from COVID and future coronaviruses that will emerge? Some, but not all research has indeed shown that people without prior exposure to CoV-2 do indeed show immune reactivity to the virus (see here and here). This means that folks who haven’t been infected with SARS-CoV-2 must have been exposed to another coronavirus that gave them a bit of cross protective immunity to the COVID virus. Other studies confirmed that prior infection with cold-causing coronaviruses can reduce COVID severity following infection with CoV-2 (here and here).

Bottom line.  What this means is that if you have been infected with some sort of mild coronavirus in the past, you just might be able to show some immunity to future infections with distant coronavirus cousins. Vaccination with the spike protein mRNA just doesn’t do the same. You need to be exposed to the whole kit and caboodle to enjoy all this immune goodness.

The responsible part of the immune system for this cross-over immune response is CD8⁺ T cells, also known as cytotoxic T lymphocytes, or CTLs. These immune cells are assassins that seek out other cells infected with a virus and they kill those cells. So, immunologists get all atwitter and think, “Hellz bellz, why don’t we make vaccines using parts of these boring, but conserved virus pieces that generate CTLs to different viral cousins, instead of the ever changing spike proteins to make vaccines? We could make one vaccine for all coronaviruses! Or flu, or whatever virus….”

It is a great idea and that research is well underway. The goal is to make a single coronavirus vaccine that would be long lasting and target many coronavirus cousins to prevent any future pandemic (believe me, another one is sure to come).

Back to earth. As interesting and hopeful as this sounds for making a single vaccine against multiple coronaviruses so we don’t have to continually try different boosters each year, don’t get your hopes up just yet. Similar immuno-optimism has been going on with influenza for decades and what do we have to show for that? We still have the annual guessing game of which flu strain will pester us each winter and then feverishly roll out millions of vaccines to try to nip that particular one in the bud. Meanwhile its flu cousins chortle and conspire in the Southern Hemisphere on how to mix and mutate their genes so they can surprise us again in the Northern Hemisphere the following year with a sufficiently new variation to vex us again.

But, flu, like coronaviruses also has important proteins that are not changeable, and very constant between distant flu cousins. These too can be seen by the immune system’s T cells. Flu immunology’s Holy Grail has long been to make a vaccine to a conserved flu virus genomic sequence so we can use just one vaccine to immunize against all flu strains once and for all for all time. A pan-flu vaccine.

Well, we are still trying to do that. This makes the idea of finding a pan-coronavirus vaccine using similar immunology daunting. Still, these recent studies showing that cross-reactive immunity between distant cousin coronaviruses does exist, just stokes an Immunologist’s stubborn resolve to solve the problem. As I have written before in these pages, amazing science advances have often come from the long, dogged pursuit of goals that very stubborn scientists believe they can see right in front of them, even when others cannot. It often takes a long time to prove what is so clearly obvious to one or two science visionaries yet so oblivious to the rest of us. That often is how science progresses. Thank goodness for these obstinate scientists who see things the rest of us cannot.

Once again, We will see.

Personal note. These anti-viral CD8⁺ or cytotoxic T lymphocytes are near and dear to this correspondent’s heart since I got my PhD in Immunology studying how these immune cells in mice recognize cells infected with viruses. It is a lot more complicated than you would think. In fact, in 1996 two immunologists, Peter Doherty and Rolf Zinkernagel were awarded the Nobel Prize for work they did on this problem in the early 70s, and that work drove my PhD research (and a lot more!).

Doherty and Zinkernagel discovered that T cells have to simultaneously identify two different molecules on an infected cell surface before they actually know a cell is infected with a virus. They made a head-scratching observation that turned viral immunology upside down. It was one of those observations that I bet made them say, “That is funny.” Basically, they found that your T cells that can recognize flu infecting your cells would not recognize flu infecting my cells or anyone else’s cells. And vice versa. You would think flu is flu and that a T cell that can see flu in an infected cell would not care whose cell it came from. But it does care. It turns out that T cells can only see virus within the genetic background from whence they came. They cannot see the same virus on a cell from a different genetic background! How strange is that? An antibody does not care where it sees a virus. T cells do. Picky little suckers.

It gets even crazier. Doherty and Zinkernagel, mapped this genetic restriction in virus recognition to the same genes that the immune system also use to determine whether a tissue or organ is its own or is foreign! For example, the genes your immune cells recognize as a password to determine friend vs foe in a skin graft (do we accept it or reject it?) are the same genes the immune cells use to help them know if your cells are infected with a virus! Tell me that doesn’t make you scratch your head and mutter, “That’s funny?” That is exactly how the world of immunology reacted to Doherty and Zinkernagel’s findings. It was a beautiful time for immunology science. That launched a tsunami of research, my PhD effort included.

This is personal note because I earned my PhD further probing the mechanism of what Doherty and Zinkernagel stumbled on. I used a large panel of mice that had been engineered to carry single point mutations in different parts of these genes that immune system used to ascertain tissue compatibility, and detect viral invasion. This helped us learn what part of these molecules the T cells recognized and how their folding was important for this recognition. It was a grand time!

Immunology is so doggone interesting!

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.

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.

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.