TWiV 711 letters

Catherine writes:

Dear TWiV team, 

Thank you so much for all the hard work you do putting together these amazing podcasts.  I just listened to episode 709 and wanted to add a clarification to your response to the letter from Deborah about the possibility that SARS-CoV2 originated in a lab.  I get the impression that Deborah and many others think the term “spillover” specifically means spillover from a lab into the population, whereas Dr. Daszak uses it to describe spillover from wild animals into the human population, and you also used it this way in your response.  I think implicitly stating that spillover does not mean something originated in a lab would help clear up some of the misunderstanding surrounding the Daszak interview.

Changing tacks, but related to the same episode,  I work in a lab where several of us have received our first dose of the Moderna vaccine.  The consensus so far is that it feels similar to getting the flu shot, except for a few people who developed cold sores soon after receiving it.  I was not one of them, but I am lucky not to suffer from cold sores at all.  I looked at the results of the clinical trials and cold sores were not listed under the adverse events, though there are several general categories they could fall under.  It could of course be a coincidence, but now we are interested to see if the same thing happens after those people get their second shots.

Keep up the good work and thanks again for all that you do, 

Best Regards,

Cat

Robert writes;

Vincent thank you.

I will write a more thoughtful email later, but I couldn’t hold back after #709!

My attention was divided toward the end with work, then the singing started!

Kathy’s singing snapped my attention back. Thanks for all your tweaks along the way to keep the show evolving, although I do miss the soothing sound of Dixon’s breathing. 

Cheers, 

Robert from San Mateo, CA.
(Just a UVC systems designer)

Martha writes:

Dear TWIVers all,

I just finished listening to episode 709. I realised I’d better send you this poem now, in case Wuhan turns out to not be the ultimate source of the SarsCov2 virus. My apologies to Lt.Colonel John McCrae, MD who wrote “In Flanders Field” in 1915 after the second battle of Ypres. As far as I know he did not write any poems related to the Flu Pandemic that occurred a few years later.

In Wuhan’s caves the virus grow
within the bats hung row on row.
They hang by day, and when they fly,
 spread poo and virus from the sky,
 scarce noted by the folks below.

We RNA virus, you know,
don’t live, but multiply and grow,
recombine, mutate and so
As we infect the host.

Take up the task, the spread to slow:
wear masks, wash hands, at distance go!
It’s on you now to fix this mess!
If your vaccines have success, 
We shall then sleep (until the next spillover).

Also apologies for anthropomorphizing. Virus don’t actually write poetry, give public health advice or sleep. And I think that use of the word ‘mutate’ is a bit dodgy. It is, however, a virus that is speaking.

Thanks for all you do keeping the public informed.

All the best

Martha

Chris writes:

Hi, TWiVvers,

I love the podcast and listen all the time. Thank you for performing a great public service!

On your most recent episode you guys discussed very nonchalantly about how mice were dosed with drugs “until they croaked,” or that kind of language.

Look, Folks (to use Bidenese), I get it: scientists studying human disease can use a lot of mice (111 million mice and rats annually in the US according to a recent study). And we do try to be ethical, follow IACUC regulations, not cause undue pain, etc. And after a while you can get used to the idea and become a bit numb to it. I can recall being called out myself for calling them “furry test tubes” when describing what I thought was a particularly gamed in vivo system.

The thing is that you are speaking to a lay audience, and that kind of dismissiveness about what are, after all, living creatures will rub people the wrong way. We always have to remember to tread lightly here. Language matters. You do not “off” or “harvest” mice, you sacrifice or euthanize them.

I am not sure if there is a hierarchy of “livingness” — you probably would not talk this way about monkeys, and maybe it’s OK with fruit flies. While I was in graduate school I used to take a shortcut through where the monkey cages were stored, and I can remember my horror at seeing children’s toys in those cages. Well, I suppose it is nice that the monkeys had toys, but it really struck me that they are not too far from us. And, well, of course it is their similarity to us that makes them useful for research.

Let’s just please be cautious, as there are people who are convinced that using animals at all is unacceptable. We do not want to make their argument easier.

Thank you for the great podcast, sorry that my first email to you is a complaint!

Sincerely,

Chris

— 

Chris Mehlin, PhD
Chief Scientific Officer
LINK Immunotherapeutics

Donnelly writes:

Hi Dr. Griffin and Dr. Racaniello,

I recently read an article by Derek Lowe in the Science mag, and he mentioned the potential for some of the lipid nanoparticle based vaccines to cross the blood brain barrier and be endocytosed by some glial cells. This in turn could then prompt CD8 T cells to attack these glial cells and potentially lead to CNS disorders such as multiple sclerosis or ALS. My question is first, how realistic is this scenario? Secondly, is it technically possible for the virus itself to infect glial cells and cause this issue? Thanks everyone at microbe TV for keeping me sane and up to date during this whole past year!

Best Regards,

Donnelly

(Here is the article in question)

https://blogs.sciencemag.org/pipeline/archives/2021/01/11/rna-vaccines-and-their-lipids

Sebastien writes:

Hi,

I listened carefully to your episode last Saturday, and I am curious to understand why a covid vaccine gives longer protection than being infected. 

If I draw some conclusion from a different disease, I myself had chickenpox, and have always been told that I am not immune to the disease. Therefore in this instance the natural course of action, is at least more efficient than the vaccine. Could you help me make sense out of this please?

Regards

Sebastien 

Joanne writes:

Dear Professor,

I am working in microbiology for a long time but new to viral culture.

I am wondering why we did for plaque assay, sometimes are normal but I cannot explain why sometimes getting weird plaque likes the photo showing at 2nd and 3rd photo. I expect most concentrated well should be mostly blue due to TNTC.

Let me explain little bit more. Those are H3N2. For 2nd and 3rd photos, we were incubated at 33°C since shared incubator with OC43 during that incubation period. Also the sampling solution was SCDLP (=TSB broth with Lecithin and Polysorbate) as we were on trial for ISO 18184 / ISO 21702 antiviral test for textile and plastic. However, 2nd and 3rd photos we were just swab the viral suspension on stomacher bag of PE plastic and even glass slide, suppose none of inhibition. 

I am suspecting this phenonemon due to……

1. Improper temp. for H3N2? Is it critical for virus culturing even 1°C different?

2. Those weird plaques incubated for 2 days instead of 3 days, time issue?

3. SCDLP broth impact to cell growing? We checked pH that is normal, we did some trial also using SCDLP but no issue. We did not see any cytotoxic effect based on other trial.

4. We are using hand shake/mix after adding viral suspension onto the monolayer plaque, is it not mixed well to cause weird results? We add viral suspension and incubate for 1 hr before adding agar, during this one hour incubation, every 15mins take out and mix again to avoid dry in some area.

Hope you can give me some insight how I can solve the issue. Thank you in advance.

Stephen writes:

Dear TWiV Team,

After your discussion on last Sunday’s episode (1/17) about the very different efficacy numbers for the CoronaVac vaccine, I saw this news about Sinovac trying to explain the variation. 

Sinovac Steps Up Defense of Shot After Confusing Data

Basically, they’re blaming the long numbers in the Brazil trial on the fact that the 2nd dose was administered in most cases 2 weeks after the 1st dose, and that the efficacy would be better after 3 weeks. Given what I’ve heard on TWiV about needing to wait 3 weeks before administering a boost dose, that makes sense (though I’d still want to see better data). 

But I have to wonder–who the heck thought trial a 2 weeks gap was a good idea if the science says you need to wait at least 3 weeks?

Thanks,

Stephen

Jesse writes:

Hello, 

I very much enjoy your show. In episode 709 there was a brief discussion of the use of laboratory animals in the production of vaccines. I believe that you could make a case that animals, though not laboratory animals, are indirectly used for vaccines in some cases. For instance the horseshoe crabs are bled (though not as much now I gather) for endotoxin tests on injected vaccines, and chicken eggs are used for injected flu vaccines. Are there other examples you are aware of these indirect uses of animals in the production of vaccines?

Best,

Jesse

Neda writes:

Dear TWiV team,

I am a long-time listener and I have so much appreciation for the hard work that is put into this very informative podcast. I am the head of the food virology laboratory at Health Canada and my team is now trying to understand the role of food and food-contact surfaces in transmission of SARS-CoV-2. There are a number of factors that suggest food could play a role in persistence and occurrence/reoccurrence of COVID-19 in some regions including remote areas in Canada, where travel was strictly restricted:

1-     30%-50% of patients experience gastrointestinal symptoms

2-     infectious viral particles are shed in patients’ stool irrespective of their symptoms

3-     SARS-CoV-2 can efficiently replicate in human and bat enterocytes

4-     SARS-CoV-2 can endure human gastrointestinal fluids.

5-     Oral inoculation of golden Syrian hamster model leads to infection of lungs and intestine

Contrary to what Rich has suggested, even classic foodborne viral outbreaks caused by noroviruses, which have a very short incubation time, cannot be easily identified let alone potential foodborne clusters caused by SARS-CoV-2 that has a long incubation time. Moreover, there is no food surveillance system for SARS-CoV-2 in North America and Europe. Importantly, COVID-19 patients are not asked to remember potential “high-risk” food that they consumed, an approach that is usually employed in foodborne viral outbreak investigations.

Kind regards,

Neda Nasheri, PhD.
Research Scientist
Food Virology Laboratory
Bureau of Microbial Hazards, Health Canada

David writes:

Hi Vincent,

You’re a stickler for correct use of terminology, but you routinely misuse the term “homology”. Homology is defined as descent from a common ancestor. Either two genes are homologous or they are not. Saying that two sequences are 50% homologous is like saying someone is 50% pregnant, it makes no sense. The correct terminology is to say two sequences are X% identical, or if you are counting conservative amino acid changes, X% similar. Every time you say these viruses are 95% homologous, you make the bioinformatics trained people in your audience gnash their teeth. And as a former director of a bioinformatic training program, I would definitely call you out on it 🙂

Best,

David

P.S. On the origin of the virus, you need to be aware that Twist BioScience and other companies offer de novo gene synthesis at $0.07 per base. Completely synthesizing a coronavirus genome would cost about $2,000, and for a very modest additional fee they will introduce degenerate sites wherever you want them. Creating a library of genome variants derived from an animal virus, transfecting them into human cells and selecting viable clones is an experiment that could be done quickly and at modest cost. A virus that was 95% identical to RatG13 with randomly dispersed changes most of which are scientifically uninterpretable is exactly the kind of thing such an experiment might produce. I fully believe that SARS-CoV-2 arose through natural processes, but with modern biotech, it’s impossible to say something could not have been artificially created.

David J States MD PhD FACMI
Chief Science Officer
Angstrom Bio
Austin, Texas