Category: medicine

My Pfizer jabs

January 27, 2021 • 10:45 am

As I’ve mentioned in passing, I’ve had two coronavirus shots; these used the Pfizer vaccine. The university hospital has been vaccinating a gazillion people, starting with healthcare workers on the front line, hospital employees, local oldsters (like me) and then residents of the South Side, mostly black, as well as healthcare workers who aren’t affiliated with the hospital but work on the South Side. It was heartening to go to the Covid clinic, an efficient and dedicated facility in the hospital, and wait in line with a cross-section of Chicago, including healthcare workers in their scrubs, all of us “in it together.” I have nothing but praise for that organization and its efficiency, and everyone was uber-friendly. I even got a “congratulations” after my second shot.

And as I stood in line, I realized what a fantastic thing these vaccines are, and, indeed, what all vaccines are.  If our immune system had no memory, if scientists hadn’t figured out that you could stave off disease by tweaking that memory, and if they hadn’t figured out how to do it without causing the disease, humanity would have been driven down over and over again.

The Pfizer vaccine is even more marvelous: a vaccine made by injecting into your arm a liquid solution of RNA “code” for the virus’s spike protein, with that code encapsulated in little fat bubbles. Once in your arm, the specially designed code makes its way to your cells, which then use the code to make many copies of the virus’s spike protein. Those free-floating copies are themselves harmless, but are the parts of the virus that adhere to cells when you get Covid-19. The immune system then recognizes the spike proteins as foreign, goes to work destroying them, and then the memory of those proteins is stored in our immune system (this is the way that all vaccines work). When you get a second shot, the immune system recognizes the spike proteins that it’s seen before, and mounts a huge defense against them, creating not only greater memory but often producing some side effects for the second jab. When you’ve mounted two defenses, your immune system is ready to go when it sees the spike protein on a virus that infects you.

In late December I wrote a post about how scientists had tweaked the spike protein’s RNA code to get it into our cells intact and make it produce many copies of the protein. That tweaking itself rested on years of molecular-genetic work done without the goal of making a vaccine. It’s a testament to the power of pure research and human curiosity.

All in all, I consider the mRNA vaccines, like the Pfizer and Moderna ones, as “miracles”—except I don’t like the word because it smacks of religion. But they do show what our evolved neurons are capable of doing when faced with a medical problem. I don’t know a secular word for “miracle”, but if there is one then it should be used with these vaccines. And remember, jabs went into arms less than a year after the virus first began its depredations in China. Further, the vaccine was designed within just a few days after the genome of the virus was decoded, which itself took less than a week.

But people want to know what the shots were like.  The first one was a piece of cake: it was a simple jab (they manage to get six doses out of a vial at the hospital, increasing the number of jabs by 20%), and I didn’t even have a sore arm. The only side effect was a very slight soreness at the injection site, but a soreness that could be detected only by pressing on the site.

It was 18 days between jab 1 and jab 2, though the usual period is 21 days. I took the shorter period because it was within CDC and Pfizer recommendations, and I was eager to become immune. I’m not sure how they know that 13-21 days is the right interval, and I don’t think they really did a lot of tests about that.

The second jab went into my arm on Monday. I was informed in great detail, and given an instruction sheet, that this jab was likely to cause more side effects, including chills, fever, muscle aches, and even vomiting. I was prepared for that: it’s better to suffer for a day or so than to get infected! I felt fine throughout Monday, but my arm was a little bit more sore than after the first jab. On Tuesday morning I also felt pretty good, and, because they said symptoms may begin within 12-24 hours, I thought I was home free.

That was not to be. At about noon yesterday (28 hours after my second jab), I begin feeling muscle aches, overall tiredness, and a general malaise, as if I were getting the flu. I recognized this as side effects and went home, dosing myself with Tylenol. My temperature, which is normally low (about 97.3° F, went up a bit, to 99.5°F). I did not lose either my appetite or sense of taste or smell, and I had a decent dinner but abjured the vino. I went to bed still feeling out of it.

But I woke up this morning feeling right as rain. As the instructions said, the side effects pass within 48 hours.  One has to wait two weeks, I understand, to acquire the vaunted 95% immunity that comes with this vaccine. From this my advice would be “when you get your injection, schedule it for late in the afternoon, go home, and then be prepared to not go to work the next day.” A Friday afternoon would be ideal for that second shot.

I asked the nurse who gave me the second jab if there was any correlation between the severity of one’s side effects and the effectiveness of the immunization. One would think that a vigorous immune response to the second dose, indicating that your immune response was quite active against the protein, would mean that you’d be better protected against the real virus. In other words, the worse the side effects, the better off you are. She said there was no correlation, as did the instruction sheet I got. I still am a bit dubious, but if there is a correlation, that I’m good to go against the virus.

Of course I urge everyone to get their jab. I asked a staff member on campus with whom I’m friends if she got the jab. I was surprised when she said “no.” When I asked why, she said because “people had died from the vaccine.” She was afraid of it, which I think is a fairly common feeling. But I looked up the deaths associated with the Pfizer vaccine, and, as we know, it’s not risky. There were six deaths during the phase 3 trials, but four of those were in the control group. Two died in the vaccine (experimental) group, one from arteriosclerosis and the other from a heart attack. Those deaths were probably the results not of the vaccine, but of underlying conditions. Of course some people will die after being vaccinated: as the control group shows, that will happen in any large group of people! On balance, though, all the experts say it’s better for your own welfare to get vaccinated than to risk Covid-19. And it’s better for society as well, since the more people who get vaccinated, the quicker we’ll attain herd immunity.

I went back to my friend and told her the statistics, but she was unmoved, and clearly didn’t want to discuss the point. Although I was concerned with her health, I realized that there was no point in arguing, as vaccination avoidance is almost a form of religion, and certainly a type of faith. I won’t bring up the subject again.

I’m sure all readers here are eager to get their shots, and it’s frustrating to watch while others get them but you can’t get an appointment. Biden and his administration are working hard on the issue. But we should be cognizant of the vaccine shortages in other countries, which are far more severe than in America or Europe. The news last night reported that America will have five times the number of doses necessary to vaccinate the entire population, and Canada six times. Couldn’t the excess be used in places like Latin America, where the Covid rate is high but vaccines rare?  I know that Bill Gates and others are donating lots of dosh to buy vaccines for poor countries, but we will need about 18 billion dollars to do that job. This is not a U.S. or European issue, but a world issue, and with the vaccine we should be far more concerned about other countries than we usually are. Even from a selfish point of view, if you don’t go after Covid everywhere, the whole world remains in danger.

I didn’t take a “vaccine selfie”; here’s the best I can do:

Summary paper on the vaccines with Fauci as senior author

January 20, 2021 • 10:45 am

Reader Simon sent me a link to this free paper about coronavirus vaccines written by several researchers, including Anthony Fauci (“senior author” means “last author”, and the convention that this spot is occupied by the Boss or lab head). It’s a useful summary of where we are, which other vaccines are coming, and what we don’t know, and is understandable by the layperson. (Here’s a link to one term you might not know: “mucosal immunity“, while “parenterally” refers to medicines taken outside the digestive tract, usually through injection.)

Click on the screenshot to read:

There’s a useful table of vaccines already used compared to those in development. Of the five remaining vaccines, three involve viruses: mostly inactivated viruses that can’t replicate but can produce the spike protein that activates your antibodies, while two others involve injecting spike proteins themselves, made in insect cells. Click to enlarge:

 

Here’s a figure I’ve posted before showing the protection you get from the two vaccines in use in America now: the Pfizer/BioNTech and Moderna formulations.

Note that you’ve already gotten substantial protection before you get to the second jab. For both vaccines the efficacy (the reduction in the chance you’ll catch the virus if exposed) is about 95%.

The paper raises several concerns about the vaccines and people’s willingness to take them.

A.)  What are the side effects? Monitoring of those injected has only taken place for several months, and there may be long-term effects we don’t know about. The authors note, though, that some of the vaccinated would have had stuff like cancer and heart attacks anyway—effects having nothing to do with the injection. The frequencies of such incidents and diseases need to be compared to those in unvaccinated groups or base rates already known.

B.) We don’t know the efficacy in some important groups, including “children, pregnant women, individuals with underlying illnesses, and those taking medications that might influence the immune response to a disease.”

C.) The duration of protection provided by the vaccines. We know that the efficacy of flu vaccines wanes substantially between six months and a year after injection. Will we have to get yearly injections of coronavirus vaccines as we do with flu shots?  Of course they will continue developing vaccines, so they will get better over time.

D.) How well do the vaccines protect against (asymptomatic) infection and transmission of the virus? We should have the answer to this question in a while, and the authors consider this the most important unknown in trying to stem the pandemic. If after injection you can get infected and not show symptoms, as well as transmit the virus, this will dramatically curtail efforts to stop the pandemic cold, and mandate different strategies, like testing those already injected.

And a paragraph from the paper, which is disturbing given that roughly half of Americans plan to get vaccinated. That is INSANE! Tell your worried friends to get their jabs, as it’s better than getting coronavirus.

The point made is that the vaccines currently in use don’t provide immunity in the mucosal membranes (as in the nose), while polio vaccine did bestow that immunity, but only if made with live weakened virus. (Current flu vaccines don’t provide it either.) Active immunity in the mucosa kills the virus in the respiratory system before it has a chance to get into the blood. The coronavirus vaccines now available don’t seem to provide mucosal immunity and, as the authors say, we need vaccines that will do that. A summary:

Given that recent polling suggests that only 40% to 60% of people in the United States are currently planning to get vaccinated, it is conceivable that without some impact on transmission, the virus will continue to circulate, infect, and cause serious disease in certain segments of the unvaccinated population. Administration of parenterally administered vaccines alone typically does not result in potent mucosal immunity that might interrupt infection or transmission. In the case of poliovirus, induction of mucosal immunity through vaccination with the live attenuated oral polio vaccine, in contrast to the parenterally administered inactivated vaccine, was thought to have played a critical role in interruption of transmission and control of poliovirus epidemics. For these reasons, additional data regarding protection from infection should be generated as soon as possible. If these vaccines do not provide durable, high levels of protection from infection, and do not drive the prevalence of virus in the community to near zero, a thorough analysis of shedding and transmission will need to be done through additional study. Armed with such data, public health officials can make decisions regarding prioritization of populations to receive the vaccine, and researchers could potentially improve upon the first wave of vaccines.

A woke Hippocratic Oath

January 15, 2021 • 11:30 am

It’s often assumed that medical students take the Hippocratic Oath when they graduate or during the “white coat ceremony“—when they get their Official Doctor Coats at orientation. In fact, there’s a report from the Association of American Medical Colleges (AAMC) that most medical students never take that famous oath, and many classes write their own. Although there are still some “standard” oaths, the AAMC notes this:

. . . it was only around 20 years ago that schools began to allow students to craft their own promises.

Nancy Angoff, MD, remembers the decision to discard Yale’s long-standing oath back in 2000. “Some students and I didn’t care for the language,” says Angoff, associate dean for student affairs. “It seemed very impersonal, cold, and too pat.” At first, they considered reverting to the Hippocratic Oath.

“We debated it,” recalls Angoff. “The students didn’t want to promise things they couldn’t deliver on” that the ancient oath included, so they opted to write their own pledge.

Now Yale is among the 17% of surveyed schools that have an annual process for writing, revising, or selecting an oath. At Yale, the oath is written during a pregraduation course, explains Angoff. Each year, she says, “the students end up with a really personal and beautiful oath.”

You can see why they’ve ditched the original Hippocratic Oath if you read it here. There are parts that are really outmoded, such as this bit, which rules out assisted suicide and abortion:

I will not give a lethal drug to anyone if I am asked, nor will I advise such a plan; and similarly I will not give a woman a pessary to cause an abortion.

Now I’m not sure why the students write oaths rather than the faculty, for the faculty surely have a better idea of what good physicianship is all about. And of course the students, who are quite young, can go hog wild, as they apparently did at Pitt. And you know already what they did—and what’s probably happening all over the U.S. They pledged themselves as doctors to engage in social-justice activism.

From PittWire, a publication of the University of Pittsburgh, we have a report of one new oath  (click on screenshot to read):

There was a committee to write an oath (always a bad idea), and they produced an oath that was sent to me by reader Ginger K., who commented, “Some of this is quite reasonable, such as the commitment to research and mentoring, collegiality, and personal health. But the woke vocabulary dilutes the good stuff.” Indeed.  The titer of real physicianship is quite low here.

Read the oath for yourself. Right off the bat I was distressed by the ubiquitous ritual invocation of George Floyd, who has nothing to do with medical school or prospective doctors (The Floyd Invocation also initiates “antiracism” statements on some of the University of Chicago’s departmental websites that violate our University principles):

One gets the impression from this statement that medicine is more a social justice mission—fixing racial inequities, fostering allyship and so on—than a mission to bring health and save lives. There’s more about social justice here, including the au courant “self care”, than there is about caring for patients per se, or practicing ethical behavior towards all patients. (And where is the confidentiality clause that was in the Hippocratic oath?)

I’m not going to make too much of this, as students probably enjoy producing their own oaths. But in the end this seems to be an act of virtue signaling, for most of the physicians will be engaged in the quotidian duties of simply helping the afflicted rather than fixing racial inequality.

I do admire those who sacrifice a comfortable existence to help the oppressed and poor, but this is an individual choice, not something to be decreed with a pledge recited by everyone.  For surely not all students agree with this oath—just like not all professors at the University of Chicago agree with their departments’ “anti-racism” statements.

Take this as a sign of the times, and of the racialization of everything. For some students it may be a genuine pledge, but for many of the others it’s performative wokeness, something to be forgotten as soon as they pass their boards.

 

h/t Ginger K

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.