My birthday trip to the dentist

December 30, 2020 • 2:00 pm

I’ll make this post short as it’s about a medical (or rather, dental) procedure.

A few days ago, an old crown on one of my lower molars popped off, and there wasn’t much tooth left (when some of it sticks to the inside of the crown, you’re screwed). The dentist was closed, but there was no pain (I later found that I’d had a root canal in the tooth), and when I called after hours my dentist told me to come in today. Of course, it was my birthday. And as I was scheduled for an hour and a half, I figured they planned to to pull the tooth. For me, that means getting an implant.

Dental implants, though pricey, are a fantastic advance in the practice. Right after they pull the tooth (which was painless for me, though time-consuming because they had to dig out the roots), they drill a titanium screw into your jaw, as well as filling the tooth hole with bone-graft material (I think they use powdered pig bone or human cadaver bone). After three months, the titanium has integrated with the bone, and they make a crown to put atop the screw. The results sort of look like this:

Afterwards, it looks and feels like a normal tooth, and requires just the usual care: brushing and flossing (though you dab a bit of disinfecting solution around it each night).

Because I have familial soft teeth (but great gums), this is the third implant I’ve had, and it’s not a big deal save the hit in the pocketbook, and the results are great. I’ve never had a problem with an implant.

I also quite like my dentist, whom I’ve had since I first came to Chicago. When they closed the excellent dental clinic at the U of C hospital, where he was head, he went into private practice and I followed him. Of all the dentists I’ve had in my life, he’s by far the best; a miminalist, a kind and skillful man, and very patient when there’s a difficult procedure, as there was today. (As he told me when I asked if he’d ever met a tooth he couldn’t extract, he replied, “The tooth never wins”.)

He’s also the official dentist of the Chicago Blackhawks hockey team, which means he has to be at every game (hockey players are always busting their teeth). I was told there’s a dental clinic in the United Center, where the Blackhawks play.

By the way, if you haven’t been to the dentist during the pandemic: things have changed. There is constant sanitizing, temperature-taking, and wearing of personal protective equipment. I was told that there have been no covid incidents in this dental practice, which has about four dentists and a passel of assistants and hygienists.

Anyway, I’m in no pain, but have to take antibiotics for a week and have a couple of stitches in the gum. At my age, it could be worse! But it is my birthday, which was noted by the receptionist with surprise when I made my next appointment. It’s not the best of birthdays, as I can’t eat and drink exactly what I want, but I’ve simply postponed the final day of Coynezaa until next week.

One problem with going to the dentist is that I pass about three Dunkin Donuts stores on the way (it’s downtown), and I can’t have a donut on my way there because I don’t want food in my mouth when I arrive, and afterwards I’m usually not supposed to eat for a while. Normally I’d treat myself to a donut after a medical procedure

But others don’t have to eschew the donuts. Rather, they chew them, and today I saw this classic scene on my way to the dentist.

Note the parking space in front is “reserved for police vehicles.”

The mRNA coronavirus vaccine: a testament to human ingenuity and the power of science

December 27, 2020 • 9:45 am

The Pfizer and Moderna vaccines are a triumph of both technology and of drug testing and distribution. But to me, the most amazing thing about them is how they were designed. Unlike most vaccines, which are based on either weakened or killed viruses or bacteria, these use the naked genetic material itself—specifically, messenger RNA (mRNA). Viral mRNA serves normally to make more viruses using the host’s own protein-making machinery, and the virus’s genome codes for the most dangerous (and vulnerable) part of the virus: its spike protein. This is the protein that, sticking out all over the virus, recognizes and binds to the host cell—our cells. That allows the virus to inject its entire genome into our cells, commandeering our metabolic processes to make more viruses, which then burst out of the cell and start the cycle all over again.

The spike protein is the dangerous bit of the virus; without it, the virus is harmless. If we could somehow get our immune system to recognize the spike protein, it could then glom onto and destroy the viruses before they start reproducing in our cells. And that’s what the Pfizer and Moderna vaccines do.

The vaccine is in fact composed not of spike protein itself, but of artificially synthesized instructions for making the spike protein. Those instructions, coded in mRNA, are packed in lipid nanoparticles and injected into our arms.  The mRNA, engineered to evade our body’s many defenses against foreign genetic material, goes into our cells and instructs our own protein-synthesizing material to make many copies of the spike protein itself.  Since these copies aren’t attached to a virus, they aren’t dangerous, but they prime the immune system to destroy any later-attacking viruses by zeroing in on the spike proteins on the viral surface.

Thus the vaccine uses our own bodies in several ways: to make copies of just the spike protein, and then to provoke our immune system to recognize them, which the body “remembers” by storing the instructions to fabricate antibodies against real viral spike proteins.  The part of this story that amazes me is the years of molecular-genetic studies that went into our ability to design an injectable mRNA, studies that weren’t done to help make vaccines, but simply to understand how the genetic material makes proteins. In other words, pure research undergirded this whole enterprise.

You can read a longish but fascinating account of how the mRNA vaccine was made at the link below at science maven and engineer Bert Hubert’s website (click on the screenshot). Hubert doesn’t go into the details about packaging the engineered mRNA into lipid nanoparticles, which is a tale in itself, so there’s a lot more to learn. At the end, I’ll link to a story about how quickly this vaccine was made—less than a week to both sequence the virus’s RNA, including the spike protein, and then use that sequence to design a vaccine based on the spike protein.  What I’ll do here is try to condense Hubert’s narrative even more. 

Before China even admitted that the viral infection was dangerous and spreading, Yong-Zhen Zhang, a professor in Shanghai, had already sequenced its RNA (the genetic material of this virus is RNA, not DNA), and then deposited the sequence on a public website (a dangerous thing to do in China). The entire viral genome is about 29,000 bases long (four “bases”, G, A, C, and U, are the components of RNA), and makes 6-10 proteins, including the spike protein.

Within only two days after that sequence was published, researchers already knew which bit coded for the spike protein (this was known from previous work on coronaviruses) and then, tweaking that sequence, designed mRNA that could serve as the basis of a vaccine. Once you’ve designed a sequence, it’s child’s play these days to turn it into actual RNA.

The final mRNA used in the Pfizer vaccine is 4282 bases long (if you remember your biology, each three bases code for a single amino acid, and a string of amino acids is known as a protein). But the vaccine mRNA does a lot more than just code for a protein. Here are the first 500 bases of the Pfizer mRNA as given by Bert Hubert, and below you’ll see a diagram of the whole mRNA used in the vaccine:


If you remember your genetics, this sequence looks odd, for mRNA sequences usually contain the bases A, G, C, and U (uracil). Where are the Us? In this vaccine, the Us have been changed into a slightly different base denoted by Ψ (psi), which stands for 1-methyl-3′-pseudouridylyl. I’ll give the reason they did this in a second.

But what you see above is less than one-eighth of the whole mRNA used in the vaccine. I won’t give the whole sequence, as it’s not important here, but the structure of the mRNA is. Remember, this was engineered by people using previous knowledge and their brains, and then entering the sequence into a “DNA printer” that can fabricate DNA that itself can be turned into virus-like RNA. Isn’t that cool? Here’s a picture of the Codex DNA BioXp3200 DNA printer used to make the DNA corresponding to the vaccine’s RNA (photo from Hubert’s site):

And here’s the heart of this post: the structure of the 4282-nucleotide string of RNA that is the nuts and bolts of the vaccine (also from Hubert):

You can see that it’s complicated. The heart of this is the “S protein__mut”, which is the engineered code for the spike protein. But all that other stuff is needed to get that bit into the cell without it being destroyed by the body, get it to start making lots of spike protein to act as a stimulus (antigen) to our immune system, and to get the spike protein made quickly and copiously. The more innocuous spike protein we can get into our body, the greater the subsequent immune response when the virus attacks. Each bit of the mRNA shown in the diagram above has been engineered to optimize the vaccine. I’ll take it bit by bit:

Cap: Underlined in the diagram above, this is a two nucleotide sequence (GA) that tells the cell that the mRNA comes from the nucleus, where it’s normally made as a transcript from our DNA. These bases protect the engineered RNA from being attacked and destroyed by our body, as it makes it look like “normal” RNA.

Five prime (5′) untranslated region (“5′-UTR”) in the diagram.  This 51-base bit isn’t made into spike protein, but is essential in helping the mRNA attach to the small bodies called ribosomes where it is turned into proteins—three-base “codon” by three-base “codon”—with the help of smaller RNA molecules called “transfer RNAs” (tRNAs). Without the 5′-UTR, the protein won’t get made. Besides helping get the engineered mRNA to the ribosomes, this region has been further engineered. First, the Us have been engineered into Ψs, which keeps the immune system from attacking the mRNA without impairing its ability to attach to the ribosomes and make protein. And the sequence has been further tweaked to give it information for making a LOT of protein. To do this, the designers used sequence from our alpha-globin gene’s UTR, for that region makes a lot of protein. (Alpha globin is one half of our hemoglobin molecules, one of the most copious and quickly made proteins in the body.)

S glycoprotein signal peptide (“sig”) in the diagram. This 48-base bit, which does become part of the protein, is crucial in telling the cell where to send the protein after it’s made. In this case, it tells it to leave the cell via the “endoplasmic reticulum”, a network of small tubules that pervades the cell. Even this short bit was engineered by the vaccine designers, who changed 13 of the 48 bases. Why did they do this? Well, they changed the bases that don’t make a difference in the sequence of the protein (these are usually bases in the third position, whose nature isn’t important in protein sequence). But these bases do affect the speed at which a protein is made. Hubert doesn’t explain why this happens, but I suspect that the engineered changes were designed to fit with more common transfer-RNA molecules (tRNAs), which are the small bits of RNA that attach to amino acids in the cytoplasm and then carry them to the mRNA to be assembled into proteins. While there are 64 three-base sequences (4³), there are only 20 amino acids that normally go into proteins. That means that some tRNAs code for the same amino acids. Since these “redundant” tRNAs are not present in equal quantities in the cell, you can make proteins faster if you design an mRNA sequence that matches with the most common tRNAs. I’m guessing that this is what these 13 changes were about.

Spike protein (“S protein__mut”) in the diagram. This is the heart of the mRNA, containing 3777 bases that code for the spike protein. In this code, too, they’ve “optimized” it by changing the “redundant” bases to allow protein to be made faster. The Ψs are now gone, as they’re not needed to evade the body’s defenses.  But there’s one bit that puzzled me until I read Hubert’s explanation. The spike protein made by the body after vaccination differs from the viral spike protein in just two of the 1259 amino acids. The engineered sequence substitutes two amino acids—both prolines—for amino acids in the viral spikes. Why? Because it was known from previous work that these prolines stabilize the spike protein, keeping it from folding up. It thus retains the same shape it has in the native virus. A folded-up spike protein may induce antibodies, but they won’t readily go after the virus’s own spike proteins because their shape is different.  This is just one of the many bits of prior knowledge that came to bear on the vaccine’s design.

The 3′ untranslated region (“3′-UTR”) in the diagram: mRNA’s have these, but we’re not quite sure what they do, except, as Hubert says, the region is “very successful at promoting protein expression.” How this happens is as yet unclear. This bit, too, was engineered by the vaccine designers to make the mRNA more stable and boost protein expression.

The poly-A tail (“poly[A]” in the diagram). This is the 140-base end of the message. All mRNAs made into proteins contain a repeat of the adenine base at the butt (3′) end, so we get an AAAAAAAAAAAAA. . . sequence. It turns out that these A’s are used up when an mRNA molecule makes protein over and over again (they’re like telomeres that get shorter as we age!). When all the As are gone, the mRNA is useless and falls off the ribosomes. Again, previous knowledge told the designers how many As to put at the end of the sequence.  It was known that around 120 As gave the best result in terms of protein production; the designers used 100 As split up with a 10-base “linker” sequence. Hubert doesn’t explain the linker, and I don’t know why it’s there.

Nevertheless, you can see the complexity of this vaccine, whose design rests on an exact knowledge of the spike protein’s sequence (recent mutations in the sequence don’t seem to affect the efficacy of the vaccine, as they probably don’t affect the spike’s shape), as well as on previous research about stuff like the Ψ bases helping evade mRNA destruction, the optimum sequences for high production of protein, the number of As at the end that are most efficacious, and then those two proline substitutions in the vaccine’s spike protein. It’s all marvelous, a combination of new and old, and a testament to the value of pure research, which sometimes comes in mighty handy.

This prior knowledge, combined with fast sequencing of RNA and the development of machines to turn code into RNA, help explain why the vaccine was designed so quickly. Of course it had to be tested and distributed as well, and this Guardian article tells you ten additional reasons why it took only ten months to go from the onset of the pandemic to a usable vaccine.

Finally, a bit of history of science is recounted by “zeynep” at Substack, showing additional reasons why the vaccine came out so quickly (click on screenshot). It’s largely about Yong-Zhen Zhang, the Chinese scientist who published the genetic code of the Covid-19 virus. Zeynep sees him as a hero who took risks with that publication. What’s clear is that without that code (and of course sequencing of DNA and RNA has been done for a long time—another benefit of pure research), we wouldn’t be near as far along as we are in battling the pandemic.

When you think about all this, and realize that only one species has both the brains and the means to make a designer vaccine to battle a devastating virus, and then think about the many scientists whose work contributed over many years to the knowledge involved in designing these vaccines, it should make you proud of humanity—and of the human enterprise of science. Yeah, we screw up all the time, and are xenophobic and selfish, but this time we overcame all that and used the best in us to help all of us.

Thanks to Bert Hubert for helping me understand the complexity of these vaccines.

Guest post: The New Yorker suggests that “other ways of knowing” can cure Covid-19

December 17, 2020 • 9:15 am

A few years ago I got an email from a colleague who was disturbed about the anti-science attitudes of the New Yorker, which include an emphasis on “other ways of knowing” —often through the arts and literature. But first I’ll repeat my colleague’s analysis:

The New Yorker is fine with science that either serves a literary purpose (doctors’ portraits of interesting patients) or a political purpose (environmental writing with its implicit critique of modern technology and capitalism). But the subtext of most of its coverage (there are exceptions) is that scientists are just a self-interested tribe with their own narrative and no claim to finding the truth, and that science must concede the supremacy of literary culture when it comes to anything human, and never try to submit human affairs to quantification or consilience with biology. Because the magazine is undoubtedly sophisticated in its writing and editing they don’t flaunt their postmodernism or their literary-intellectual proprietariness, but once you notice it you can make sense of a lot of their material.

. . . Obviously there are exceptions – Atul Gawande is consistently superb – but as soon as you notice it, their guild war on behalf of cultural critics and literary intellectuals against scientists, technologists, and analytic scholars becomes apparent.

Today’s topic, though, is “other ways of knowing through folk wisdom“. In particular: ways of healing used by indigenous people. Now this shouldn’t be rejected out of hand; after all, many modern remedies, like quinine, derive from plants used by locals. But that doesn’t imply a wholesale endorsement of “the collective lived experience” touted in this video about plant-based healing. For the “collective lived experience”, after all, sometimes includes shamanism and, in the example below, “spiritual elements” as a way of curing disease. And here the disease that “lived experience” tackles is something the Siekipai of Ecuador have never experienced: Covid-19.

Reader Jeff Gawthorpe saw a New Yorker video at the link below; I’m not sure whether you’ll have free access, but you will using the yahoo! finance link at the bottom, where the video was republished.

Jeff is about as distressed as I by the fulminating wokeness of the magazine and delivered his critical “review” of the video, which I asked if I could put up in full, including his name. (I don’t like paraphrasing other people’s words, especially when they’re as good as the analysis below). Jeff said that was fine, and so here is his take, indented. I have to say that I agree with it, and have a few comments of my own at the bottom.

Around 30 minutes ago I happened across a dreadful video on the New Yorker‘s website, which drove my temptation to meet head with keyboard through the roof. This piece of ‘journalism’ was entitled: “Fighting COVID-19 with Ancestral Wisdom in the Amazon”. And yes, It’s as bad as it sounds: unscientific, irresponsible nonsense. Complete tosh.

The message which the piece attempts to convey is that COVID-19 can be dealt with by ‘lived experience’, ancient ‘ways of knowing’, and a few bits of boiled tree bark. Then, if you hadn’t had enough already, Just before the end, a caption pops up saying: “With a new stock of plants, the Siekopai are prepared to address future outbreaks of the virus according to their traditions.” Urrrhhgg.

You’ll notice that they are canny enough to maintain a degree of plausible deniability by making no definite claims. To me this demonstrates the very worst of journalism:

  • Conveying mistruths to support an ideology
  • Lacking the courage to commit to claims by asserting them as supportable facts

That’s bottom of the barrel journalism at the best of times, but now it’s irresponsible, reckless even. It presents a clear message that indigenous knowledge and ancient wisdom are perfectly acceptable ways of dealing with the pandemic. At no point is it mentioned that these ‘remedies’ are not backed by evidence, clinical or otherwise.

As you know, many western societies have huge anti-vax movements which often distrust and denounce mainstream medicine. Unfortunately, this video just adds fuel to the anti-vaxers fire. By failing to mention that these plant ‘remedies’ have zero efficacy, they are providing implicit support to the anti-science, anti-vax groups. Worse still, they are acting like digital snake oil salesmen, imbuing members of the public with false confidence that that they can avoid or fight off this virus with a couple of well chosen tree bark specimens. It’s dangerous, irresponsible nonsense.

Click below to see the video:

My own comments are few. First, it looks like the “remedy” includes cinchona bark, the source of quinine, as a palliative (the remedy seems directed at symptomatic relief rather than a cure).

Second, even “lived experience”, while useful, is no substitute for double-blind clinical trials. Granted, the Siekipai can’t do that, but they sure as hell should take the vaccination when it gets to them.  And, like Jeff, I think it’s totally irresponsible of The New Yorker to present this video without any kind of caveat. After all, when Trump skirts the truth, they don’t hesitate to correct him.  I guess “lived experience of indigenous people” is a different matter—it’s not as if they’re recommending drinking bleach or anything.

My doctor’s new post about the Pfizer vaccine: your questions answered (and you can ask the doc if you have others)

December 14, 2020 • 10:15 am

My GP, Dr. Alex Lickerman, has once again put up a coronavirus post on his practice’s website, and allowed me to reference it here. It’s timely because it’s all about the new Pfizer vaccine. (A ICU nurse in New York may have been the first to get the shot.) How effective is it, and how do we know that? Is it safe? What about kids under 16, who weren’t part of the clinical trials? And pregnant women, who also weren’t tested? Since this is a mRNA rather than a killed-virus vaccine, should we have extra concerns about safety? What adverse reactions have been reported? If you were already infected, does the vaccination also reduce your risk of getting reinfected?  When will “normal” people who aren’t healthcare workers or nursing-home patients be able to get their jabs?

Alex has kindly agreed, as he has before, to answer readers’ questions about the new vaccine, so put your questions in the comments section below and he’ll address them as he has time. Alex has read all the relevant scientific literature, as well as the data from the vaccine trials, so ask away! But do read his 4-page summary beforehand, as it has a lot of information.

I’m not going to put up his whole post; you can go to his site to see it,  which you can do by clicking on the screenshot below:

I’ll just post Alex’s recommendations, followed by his list of “unanswered questions” (indented). The short message: GET THE SHOT AS SOON AS YOU CAN!

CONCLUSIONS

  1. The vaccine is highly effective in preventing symptomatic COVID-19 infection.
  2. The vaccine is safe. Adverse reactions, both local and systemic, are mostly minor. Though the study hasn’t yet gone on long enough to prove there are no serious long-term adverse affects, such adverse affects, if they exist, are likely to be rare and non-life-threatening based on other Phase I and II studies of other RNA vaccines.
  3. We recommend everyone who is eligible to receive the vaccine should receive it when it becomes available to them.
  4. It very well may take all of 2021 to get everyone who’s willing to be vaccinated to receive the shots, which means it likely won’t be until early 2022 that life returns to pre-pandemic normal. In the meantime, continue to wear a mask when indoors with anyone you don’t live with, wash your hands frequently, and refrain from dining indoors at restaurants.

UNANSWERED QUESTIONS

  1. While suggested by the study, still left unproven is whether BNT162b2 [Pfizer’s name for the vaccine] prevents severe COVID-19 infection, whether it prevents COVID-19 infection after just one dose, and whether it prevents COVID-19 infection in subjects who’ve already had COVID-19.
  2. The study didn’t look to see if the vaccine prevents asymptomatic infection. Nor did it assess whether subjects who developed COVID-19 despite vaccination are less likely to transmit the virus. Thus, it’s not yet clear how effective the vaccine will be in containing the spread of the infection.
  3. The study hasn’t gone on long enough to tell if subjects who were vaccinated yet still contracted COVID-19 have a lower risk of long-term effects of COVID-19.
  4. We don’t yet know if the vaccine reduces the risk of dying from COVID-19.
  5. There was insufficient data to draw conclusions about safety and efficacy of the vaccine in children younger than 16, pregnant or lactating women, and patients who are immunocompromised.
  6. We don’t yet know how long immunity lasts and whether or not booster shots will be necessary.

Pfizer vaccine deemed safe and effective by the FDA, and a question for readers

December 8, 2020 • 8:45 am

Ripped from the headlines of CNN!  Click on the screenshot to read:

Many of us know that the FDA is meeting Thursday to decide whether to approve the Pfizer vaccine for general use. If the approval occurs, vials of vaccine will be making their way across the U.S., ready for immediate transfer into the arms of Americans.

Now, judging by the headline above, it looks almost certain that the FDA will indeed approve the vaccine in two days, and the first ranks of Americans will start getting vaccinated. Who gets it first appears to vary from state to state, but, rightly, healthcare workers and nursing-home patients (and their carers) will almost always be the first in line—and that’s what the FDA recommended as well.  After all, if the vaccine is safe and effective, why wouldn’t it be approved?

The good news gets even better: it appears that some immunity is conferred even after the first dose, which appears by itself to be 50% effective (two are required for the 95% effectiveness). Flu vaccine—the single shot we should all have gotten already this year, is only between 40% and 60% effective. “Effectiveness” is the reduction of risk that you get when you are vaccinated.

From CNN:

An advisory committee to the US Food and Drug Administration on Tuesday released a briefing document detailing data on Pfizer and BioNTech’s Covid-19 vaccine candidate, which will be considered this week for emergency use authorization in the United States.

The document confirms that the vaccine’s efficacy against Covid-19 was 95%, occurring at least seven days after the second dose – an efficacy that had been previously reported by Pfizer. The proposed dosing regimen for the vaccine is to administer two 30-microgram doses 21 days apart.

However, the document also notes that the vaccine, called BNT162b2, appears to provide “some protection” against Covid-19 following just one dose.

The document describes the efficacy of Pfizer’s vaccine in the time between the first and second dose as 52.4%, but the document notes that “the efficacy observed after Dose 1 and before Dose 2, from a post-hoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the time of observation is limited by the fact that most of the participants received a second dose after three weeks.”

In other words, “the trial did not have a single-dose arm to make an adequate comparison.”

The document goes on to detail the safety profile of the vaccine as “favorable” and notes that the most common adverse reactions to the vaccine have been reactions at the injection site, fatigue, headache, muscle pain, chills, joint pain and fever.

Severe adverse reactions occurred in less than 4.6% of participants, were more frequent after the second dose and were generally less frequent in older adults as compared to younger participants, according to the document. The document adds that swollen lymph nodes also may be related to vaccination.

That’s good enough for me, and I’ll be taking the shots as soon as my doc recommends it—which I presume will be as soon as I’m permitted to get them.

A STAT-Harris Poll published last month, however, showed that the proportion of Americans willing to get vaccinated depends on the vaccine’s efficacy, but only weakly.  Below are those data in graphic form.  What’s disturbing is that if the vaccine were 50% effective, only 60% of Americans would be likely to get the shots. And even with over 90% effectiveness, which is the case with all the vaccines about to hit the market, the willingness rises to only about 63%—a pathetically low figure. I’ve heard that the acquisition of herd immunity in the U.S. to coronavirus requires that 70% of Americans have immunity; even counting those who were infected, the figures on willingness to get vaccinated doesn’t give us that level of immunity. However, it will protect those smart people who get the shots.

So here’s the question: assuming you can get the shots because you don’t have a condition that bars them, are you going to get vaccinated? (I’m assuming that the Pfizer vaccine, or one with similar effectiveness, is the one on offer.) If not, why not?

Thanks to an American Catholic bishop, the pandemic gets a boost

November 20, 2020 • 9:00 am

I was going to say “the Catholic Church gives the pandemic a shot in the arm,” but that would have been confusing. Reader Bill sent me this link to the Los Angeles Times about a faith-soaked Catholic bishop (click on screenshot) who’s bad-mouthing coronavirus vaccines because they’re supposedly made using embryonic tissue from aborted fetuses or from surplus embryos used during in vitro fertilization (IVF) that are eventually discarded.

An excerpt:

Citing ethical concerns about the use of fetal cells in vaccine development, Bishop Joseph Brennan of the Diocese of Fresno is urging Catholics not to “jump on the COVID-19 vaccine bandwagon.”

In a video shared by the diocese this week, Brennan said that some of the researchers racing to produce a coronavirus vaccine have made use of cells derived from an aborted fetus, and perhaps other “morally objectionable” materials.

“I try to maintain a joyful spirit, so I don’t like to rain on anyone’s parade,” Brennan said. “But I’m going to rain on a parade today: the vaccine parade.”

In his message, Brennan said the use of fetal cells at any stage of a vaccine’s development means Catholics cannot avail themselves of its scientific results.

“I won’t be able to take a vaccine, brothers and sisters, and I encourage you not to, if it was developed with material from stem cells that were derived from a baby that was aborted, or material that was cast off from artificial insemination of a human embryo,” he said. “That’s morally unacceptable for us.”

. . . Brennan said he is not opposed to vaccines in general, and noted that he has received vaccines for the flu and pneumonia, but said he is specifically opposed to vaccines derived from babies “whose lives were taken.”

This is one example of the hypocrisy of Catholicism. Even if vaccines were made using fetal or embryonic tissue, that tissue would eventually be discarded. Why not use it to save lives? Further, even if you think that discarding unused IVF embryos, or aborting fetuses, is “murder,” there is no evidence that women will undergo these procedures in order to help create vaccines.  Bishop Brennan has a bizarre kind of calculus in which tissue already available cannot be used to save other lives. Note that he is in general expressing the position of the Catholic church, though I don’t think the Pope has yet weighed in on this.

But are the vaccines really made using this kind of tissue? Nope—not one mentioned by Brennan during his video homily:

He cited the Pfizer vaccine by name, which — along with another vaccine from Moderna — has been roundly celebrated as a breakthrough in the fight against the coronavirus.

Brennan did not explain why he singled out Pfizer’s COVID-19 vaccine for criticism. There is no indication that it was developed using either fetal cells or human embryonic stem cells.

“Not a single stage has had it,” Pfizer spokeswoman Jerica Pitts said Thursday.

The Pfizer and Moderna vaccine candidates are made with a snippet of the coronavirus’ genetic code, and both are estimated to be roughly 95% effective.

You think the good bishop would have done his homework, for how many Catholics that heard his homily are going to check for themselves?

It is true that some vaccines are made using fetal tissue:

The Charlotte Lozier Institute, an antiabortion organization, has flagged five COVID-19 vaccine candidates that were developed with the help of fetal cells. One of them, developed by Oxford University and AstraZeneca, is in late-stage testing. So is another developed by Johnson & Johnson.

If Catholics are worried about burning in hell if they take a vaccine developed this way, all they have to do is take the Pfizer or Moderna vaccine. But I repeat: even if you equate abortion or unused IVF embryos as “murder”, what is the moral objection to using that tissue to save further lives? It’s not as if women get IVF and abortions for the purpose of creating vaccines, or get paid to do so. Those abortions or IVF procedures would take place with or without a vaccine being developed.

All I can say is that it’s a good thing that at least some vaccines are being developed without use of fetal or embryonic material, because otherwise pious Catholics wouldn’t be able to get vaccinated, and more people would die in the name of a senseless “morality”.

Allow me to regale you with details of my operation

November 4, 2020 • 9:45 am

Yesterday I had a redo of inguinal hernia surgery, which I originally had in August of 2019. When there was a swelling at the site later, I assumed it was a seroma (an accumulation of fluid at the site), and since seromas often take a while to go away, I wasn’t worried. But it didn’t go away, so I had an ultrasound, revealing that the damn hernia had recurred. My surgeon, who’s top notch, was really peeved at this, as he said that in his entire career he’d never had such a recurrence, and had no idea why. (He added that yesterday’s operation would reveal the cause.)  Inguinal hernias are the maladaptive result of our having evolved as quadrupeds and then become bipedal, but their status as “vestigial pathologies” doesn’t hearten me much.

I scheduled surgery at the U of C hospital as soon as possible, as I don’t want the damn thing there (it could get strangulated, which can kill you), and there’s always the possibility that they’d stop elective surgeries if the pandemic recurs big time.

So I went under the knife (actually three of them) yesterday.  Because my surgeon had a complicated procedure before taking me, I waited 3.5 hours in the lobby, and then, after I was moved into pre-op, where they put their initials on the hernia (to ensure they operate on the correct side), connect you to IVs, give you a slight tranquilizer, a blood thinner, and IV fluids, and make you take off all your clothes except for that damn gown that opens in the rear—I waited another two hours. Everyone was very nice, but I was bored to tears.

Finally came the moment of truth, when they wheeled the gurney into the operating room. That always gives me a perverse kind of thrill, as it reminds me of Ben Casey and Dr. Kildare, and I’m always curious to have a look at the operating room, which contained the giant laparoscopic robot, before they put me to sleep. It was crowded with people, and the big robot with its three giant cutting and manipulating arms loomed in the theater:

The surgeon sits at the console on the other side of the room as in the photo, manipulating the arms, which made three holes in my belly (they always do the middle as well as the non-hernia side to see if there’s any issues there). Robotic surgery is one of the more amazing and salubrious medical innovations of our time.

My original surgery was done by the robot, and the surgeon told me that the chances were very high that the redo would also involve minimally invasive cutting. But, he added, there was about a 15% chance that I’d have to have the “old” procedure, which involves a big incision and a much longer healing process. Fortunately, the robot did the trick this time.

Just before they wheeled me into the OR, they gave me an injection that, said the anesthesiologist, would make me forget stuff. I asked him why, and he said that many people don’t like to have memories of going into surgery. But I didn’t forget stuff: I remember every word said to me while they filled my lungs with oxygen and were preparing to knock me out. There were two men in the room and four women, including a female medical student (I had to give permission for the  student, which I did), but I realized that they were going to see me naked. This was brought home to me when I woke up almost completely shaved in the nether parts. Oy!.

I was particularly interested to experience the loss of consciousness. Would it be nearly instantaneous, like last time when everything went black at once? It was even faster this time! I remember the anesthesiologist approach me on the left side, and I asked him “Is this going to knock me out?” He replied “Get ready for the happy juice!” (What a card!). And that’s the last thing I remember; I don’t even remember losing consciousness. (By the way, the fact that consciousness is completely removed, even without dreams, with propofal—the “Michael Jackson drug”— and then restored within ten minutes after surgery, is strong evidence that consciousness is a purely physical phenomenon.)

I woke up almost instantly; the operation, I was told, took about two hours. I was groggy for a while, but just wanted to get my tuchas home. Within an hour a friend picked me up and I got back to my crib, lying in bed for a short while and then making some soup. When I felt more restored, I took this selfie of my shaved belly (trigger warning: shaved belly!) The curious thing is that I did forget things during post-op: I called several friends today to tell them I was all right, and a few informed me that I’d already called them last night.

Note that they shaved me bald (the depilation went much lower), and that there are three punchholes, all closed with a superglue-like material. That’s the only scarring, and when the hair grows back they’ll be invisible.

I had some slight pain during the night, but regular Tylenol took care of that. I had no prescriptions for antibiotics or other pain meds, as they also gave me an IV antibiotic in pre-op.

So, Ceiling Cat willing, that is the end of this procedure. I didn’t get to talk to the surgeon yet, though I’m just as curious as he was about why the damn thing recurred.

Thanks so much to all the kind people who took care of me, from pre-op through recovery. Special thanks to Dr. Vivek Prachand for his compassion, his willingness to answer questions, and his and steady hand at the robot. Like Dan Dennett, I say, “Thank goodness!”

Covid 19 may hijack pain receptors, reducing pain and increasing the spread of the virus: a possible result of natural selection

October 8, 2020 • 9:00 am

The paper below, which has just been published (click on screenshot to go to page, then click the “download” button to the left to get the pdf), has a unique twist that may say something about evolution in pathogens, but the evolutionary angle hasn’t been mentioned. It’s a complex and technical paper, using rat models (i.e., tissue and analyses), to study whether the Covid-19 virus has the ability to reduce pain.

There’s also a publicity piece from the University of Arizona that explains the results in simpler language, and a two-minute video below that dumb things down a bit, but gives the gist.

From the publicity piece:

SARS-CoV-2, the virus that causes COVID-19, can relieve pain, according to a new study by University of Arizona Health Sciences researchers.

The finding may explain why nearly half of all people who get COVID-19 experience few or no symptoms, even though they are able to spread the disease, according to the study’s corresponding author Rajesh Khanna, PhD, a professor in the UArizona College of Medicine – Tucson’s Department of Pharmacology.

Rajesh Khanna, PhD. (Photo: Kris Hanning/University of Arizona Health Sciences)“It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” said Dr. Khanna. “You have the virus, but you don’t feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that’s of enormous value.”

The paper, “SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia,” was published today in PAIN, the journal of the International Association for the Study of Pain.

. . .The U.S. Centers for Disease Control and Prevention released updated data Sept. 10 estimating that 50% of COVID-19 transmission occurs prior to the onset of symptoms and 40% of COVID-19 infections are asymptomatic.

“This research raises the possibility that pain, as an early symptom of COVID-19, may be reduced by the SARS-CoV-2 spike protein as it silences the body’s pain signaling pathways,” said UArizona Health Sciences Senior Vice President Michael D. Dake, MD. “University of Arizona Health Sciences researchers at the Comprehensive Pain and Addiction Center are leveraging this unique finding to explore a novel class of therapeutics for pain as we continue to seek new ways to address the opioid epidemic.”

In other words, the virus’s famous spike protein nullifies the effect of another protein, VEGF—one of the several proteins that normally causes pain. And that’s all ye need to know unless you work on this system.

But here’s where the evolution comes in. Remember, pain is an adaptation whose evolution was doubtlessly prompted by its ability to tell us that there’s something wrong, like “Hey, your hand is in the fire.” People who don’t feel pain, like those with Hansen’s disease (leprosy) and some rare neurological conditions, often incur severe damage to their bodies because they’re unaware of injuries. The reason Hansen’s sufferers lose their fingers and other bits is not because the bacteria eat away at those bits; rather, it’s because the bacteria numb feelings of pain, and so you start damaging your body without being aware of it. So pain is a good thing to have, even though it feels bad.

But if a virus that normally causes pain because it injures your innards can somehow block that pain, it might spread faster. This would be true for viruses like COVID-19, which is spread by human-to-human contact, and depends on its transmission for people going about and infecting others. If you take to bed because you’re in pain, the virus won’t spread as well.

And what that means is that mutant variants of the virus that reduce pain will spread faster than forms that cause pain. This differential would create natural selection for the mutants that reduce pain, and the virus “species” would evolve painlessness as one “symptom”.

As far as I can see, nobody in either the paper or the puff pieces have mentioned this possibility. Now we don’t know if this speculation is true, or if it’s just fortuitous that the spike protein blocks pain receptors. Further, while this might be an evolved property of the virus, it could also be an inherent property of the spike protein, evolved for other reasons, that simply allowed the virus to spread quickly.

I’m merely suggesting this as one possibility in a field called “Darwinian medicine,” which analyzes symptoms of diseases from an evolutionary viewpoint. Other suggestions from this area involve things like malaria. When you have a malaria outbreak, the malaise and fever put you flat on your back. And that facilitates the spread of the malaria pathogen (a protozoan), because that protozoan is transmitted by mosquitoes. When you’re prostrate in bed and sick, you’re not as liable to slap a biting mosquito as when you’re walking around, and so those protozoans that knock you flat will more readily find a mosquito vector. (This is all speculation, of course.)

Another suggestion involves the virus for the common cold. It doesn’t debilitate you, but rather makes you a bit grotty but still able to walk around—and transmit the virus to other people. If a common cold were to knock you out like malaria, the virus wouldn’t spread so well.

And so many of the symptoms that are caused by pathogens may well have evolved in those pathogens to facilitate their own transmission. This must certainly be true in some cases, but of course proving it is very hard to do. You couldn’t do experiments in humans, though I suppose you could in model animals like rats, but I wouldn’t be keen on hurting animals to test evolutionary hypotheses. (I even anesthetized all my fruit flies before killing them.) It is curious, though, that I haven’t seen this new and striking result mentioned as a possible example of natural selection in the virus.

Here’s the video, though you might not learn much if you’ve read what’s above.

h/t: Charles

Click to access 2020.07.17.209288.full.pdf

Nobel Prize for Physiology or Medicine goes to three for discovering the Hepatitis C virus

October 5, 2020 • 7:00 am

Knowing that the first Nobel Prize for science would be awarded today—in Physiology or Medicine—I made a contest in which readers were to guess just one winner of each of the three science prizes plus the winner of this year’s Literature Nobel.

Well, the first prize was awarded this morning, and the contest is already over. Everyone lost (see here and here).

Granted, this was not an easy one to guess. The award in fact went to three people—Harvey Alter, Michael Houghton, and Charles Rice—with each getting a third of the prize money. The award was given for the discovery of the virus that causes Hepatitis C.  Here’s part of the press release from the Nobel Prize site:

This year’s Nobel Prize is awarded to three scientists who have made a decisive contribution to the fight against blood-borne hepatitis, a major global health problem that causes cirrhosis and liver cancer in people around the world.

Harvey J. Alter, Michael Houghton and Charles M. Rice made seminal discoveries that led to the identification of a novel virus, Hepatitis C virus. Prior to their work, the discovery of the Hepatitis A and B viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives.

. . . The Nobel Laureates’ discovery of Hepatitis C virus is a landmark achievement in the ongoing battle against viral diseases (Figure 2). Thanks to their discovery, highly sensitive blood tests for the virus are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the world, greatly improving global health. Their discovery also allowed the rapid development of antiviral drugs directed at hepatitis C. For the first time in history, the disease can now be cured, raising hopes of eradicating Hepatitis C virus from the world population. To achieve this goal, international efforts facilitating blood testing and making antiviral drugs available across the globe will be required

Here’s the video of the award with details about the winners, and giving some scientific background; the action starts at 12:50. It’s worth listening to the 20 minutes of science, as you’ll learn a lot. There’s also an interview with the Secretary of the Prize Committee beginning at 34:34.

I guess the prize for CRISPR-Cas9 will have to wait for another year.

A good article on Covid-19 testing, a way forward, and where we screwed up

October 2, 2020 • 1:45 pm

I commend to your attention this article in The Atlantic on Covid-19.  The authors, Robinson Meyer and Alexis Madrigal (staff writers on science and technology), discuss the best ways to stem the pandemic, the advantages and disadvantages of various tests for infection, and how the U.S. screwed up in its response. Click on the screenshot to read:

It’s very good and clear on the science, though I can’t judge the efficacy of their plan, which involves continual “spit testing”, a very quick but not completely accurate way of diagnosing the virus through its antigens, like the spike protein. PCR tests are much more accurate, but are expensive and take time, yet if we do continual antigen testing, the errors tend to go away, and we could get results in 15 minutes on a strip of paper. You could do this before flights, before entering restaurants, and so on.

The problems with PCR tests are numerous, the most serious being that it can’t distinguish between a new infection, which is contagious, and one that’s a month old, which isn’t contagious. And they’re much more expensive to distribute and more time-consuming to diagnose. The authors discuss “pooling”, a cute way to cut down on money and time by bundling together swab results (or spit) from a bunch of people. If there’s no positive in the mix, you needn’t go further. If there is, you subdivide, and so on.

The main reason we screwed up is, of course, Trump. In this case the authors indict him for failing to invoke the Defense Production Act, a wartime regulation, still on the books, that allows the government to force companies to mass-produce things in case of a national crisis, like this one. One excerpt:

. . . the Trump administration has addressed the lack of testing as if it is a nuisance, not a national-security threat. In March and April, the White House encouraged as many different PCR companies to sell COVID-19 tests as possible, declining to endorse any one option. While this idea allowed for competition in theory, it was a nightmare in practice. It effectively forced major labs to invest in several different types of PCR machines at the same time, and to be ready to switch among them as needed, lest a reagent run short. Today, the government cannot use the Defense Production Act to remedy the shortage of PCR machines or reagents—because the private labs running the tests are too invested in too many different machines.

Because of its trust in PCR, and its assumption that the pandemic would quickly abate, the administration also failed to encourage companies with alternative testing technologies to develop their products. Many companies that could have started work in April waited on the sidelines, because it wasn’t clear whether investing in COVID-19 testing would make sense, Sri Kosaraju, a member of the Testing for America governing council and a former director at JP Morgan, told us.

The Trump administration hoped that the free market would right this imbalance. But firms had no incentive to invest in testing, or assurance that their investments would pay off. Consider the high costs of building an automated testing factory, as Ginkgo is doing, said Stuelpnagel, the Illumina co-founder. A company would typically amortize the costs of that investment over three to five years. But that calculation breaks down in the pandemic. “There’s no way that we’re doing high-throughput COVID testing five years from now. And I hope there’s not COVID testing being done three years from now that would require this scale of lab,” he said. Companies aren’t built to deal with that level of uncertainty, or to serve a market that would dramatically shrink, or disappear altogether, if their product did its job. Even if the experimentation would benefit the public, it doesn’t make sense for individual businesses to take on those risks.

So nothing happened—for months. Only in the past few weeks has the federal government begun to address these concerns.

Even if you don’t see the use of mass antigen testing as a big step forward until (and if) we get an effective vaccine, this article will teach you a lot.