Melanie writes:

Boxing mice?

Hello everyone,

I hear knock-out mice talked about often and how they have helped researchers understand viruses. Will you please explain who makes them and how you get them? They are such an important part of research and I know very little about them. Thank you.

Curious in California,


Rebeca writes:

Dear TWIV Team:

First, thank you for your time and efforts on this podcast. It has kept me sane this last year.  I try to listen to the recent episodes and sneak in past episodes to catch up on the backlog I missed prior to discovering you in February 2020. Thanks from my dog too… she gets in more walks. 🙂

I’m just a technology professional who also instructs at a Private Northern California University. This means the conversations you have around schools and specifically universities always catch my interest and has direct relatability to my every day. 

I wasn’t sure if you saw this Post, that Rutgers is going to require COVID-19 Vaccine?

I know this has been a topic at my university, but so far our Leadership keeps saying we cannot require it due to only having EUA. Love to hear your thoughts.

It is a beautiful 52 F morning in California. 

Stay safe!



Patricia writes:

Good morning TWIV team! 

A balmy 56° here with cloudy skies and rain in the forecast this morning in Saratoga Springs, NY.

Later this morning (8am) I’ll be meeting with my Virology students by zoom to discuss the recent TWIV episode #734.  TWIV is a core part of our Virology course curriculum, and I reserve a big chunk of our Friday class meetings for a discussion of the most recent TWIV.  Today will be fun!

On the recent episode with guest Susan Weiss, she described the paradoxical situation of detecting viral RNA with no other indication of active infection- as if the viral RNA was somehow specifically stabilized.  It made me think that the stable viral RNA detected might be a form of circRNA. 

I did a quick search earlier this morning and found this preprint on bioRxiv from December 2020 “Circular RNA profiling reveals abundant and diverse circRNAs of SARS-CoV-2, SARS-CoV and MERS-CoV origin” by Yang et al on bioRxiv.

Once considered an inconsequential and minor by-product of splicing- circRNAs are incredibly abundant and diverse- with evidence that some may be able to function as messenger RNA or other regulatory RNA molecules.  Might be worthy of a future TWIV!

Here is the link to the preprint- I’m keeping an eye out for the peer-reviewed version!

All the best,

Pat Hilleren,
RNA Biologist, Assoc. Professor in Biology, Skidmore College

Masa writes:


Thanks for a great show!

You discussed the vaccine situation in Europe a bit, and I can give you some more details.

EU handled vaccine procurement as a bloc. So they bought vaccines for all the EU countries. However, they acted late with most vaccines. During 2020 US was almost always first to order from all the companies. The US procurement was aggressive and yielded the best results.

Companies seem to serve the countries first come first served basis so the EU gets the shortest straw most of the time. There were also some other hiccups. Firstly the GSK/Sanofi vaccine failed, which removed a large part of supply. Then the Astra Zeneca vaccine faced massive production problems in EU plants decreasing the output. AZ has other plants, but for various reasons, there are no vaccine imports into EU.

Meanwhile, EU has exported 40 million doses to various countries from EU based plants. It has received none. This is partly because of export restrictions set by Biden administration and the Boris Johnson administration.

One of the most frustrating details is that J&J plants in EU can’t send product to US for fill & finish because it’s likely that with Biden’s export ban the finished product couldn’t be sent back. This has caused delays in the J&J rollout as they’ve had to scramble for capacity in the EU. Allowing fill & finish export wouldn’t even affect the US vaccination program a bit. To be frank, this single case seems quite evil from Biden.

I can understand that Joe Biden wants to bask in the vaccination glow, but is it truly right that high risk people in their 60s and 70s are without vaccines in the EU, while US is vaccinating people under 30? 

The risk for someone in their 70s vs. 30s is completely different. EU has also one of the oldest populations on the planet, so the vaccine deprivation is really hurting people here. The daily death rate is roughly around 2-3x higher than US at the moment.

My 69-year old father with high risk comorbidities will be vaccinated maybe in April. I hope he survives until then.

It seems EU is now starting its own export bans if the situation does not improve. This will probably hurt everyone. However, it’s hard to explain to people why vaccines are taken away from EU into countries who are vaccinating young people.

If you can, please try to advance solidarity in your administration. The US export ban is most likely killing elderly people in EU unnecessarily, because the vaccine rollout has been slowed out even further because of extremely strict export bans by the Biden administration.

Thank you!


Kim writes:

Hello TWiV team!

First, an immense thank you for your team for your never ending pursuit of accurate information and sharing your knowledge with us, the public! And to do so in such a convivial manner, as your team does, makes learning an absolute delight 🙂

Second, the intro with Arturo Casadevall was truly fantastic. Speaking up and being transparent about our larger problems in science always seems to trigger a bad reaction from the group at large. But as scientists, isn’t it our goal to improve not only our understanding of the natural world around us but also the way in which we study it? Really great to hear this topic on your platform.

Lastly, I have a favor to ask re: terminology about plasma and serum. Plasma is the protein-rich liquid fraction of your blood. The other components being cellular material (white blood cells, red blood cells, and platelets). Plasma contains molecules important for immune function (e.g. antibodies and complement proteins) as well as hemostatic function (proteins in the coagulation pathway (e.g. Factor II (AKA thrombin) and fibrinogen) and clot formation (e.g. von willebrand factor)). Serum is generated from plasma through inducing coagulation. This causes consumption of all of the clotting factors, such that serum is in essence plasma devoid of clotting factors. Serum still contains the immune aspects of plasma.  

COVID-19 convalescent plasma (or CCP) is in fact plasma, not serum. It contains large amounts of coagulation factors (e.g. Factor II, fibrinogen) that are transfused alongside the SARS-CoV-2 antibodies. CCP is not processed to the level of serum. Can the team please be sure to refer to CCP as plasma and not serum? Sorry for a seemingly trivial verbiage request, but these two terms are not really interchangeable, and in the case of the thrombotic complications associated with COVID-19, I think it is important to be clear about the coagulation potential of plasma.

Thank you so much for interviewing Arturo! I share his enthusiasm for the role of antibodies in the vascular space. A while back you all discussed a paper from Vidarsson’s group about how alternative glycosylation patterns on SARS-CoV-2 antibodies altered antibody function – also an area of research I enjoy. Would have loved to hear Arturo’s take on CCP and glycosylation.

Keep up the incredible work, and know you are all greatly appreciated!

Wishing everyone the very best,


just an immunologist who dabbles in alloimmunity, transfusion medicine, and hemostatic resuscitation…. so as Arturo says, I find it hard to pigeonhole myself 🙂

Sarah writes:

Hi TWiV, 

I always listen with interest to your episodes and learn a lot. I have a question about episode 739 on April 4 because I think you are wrong in how you characterize randomized trials for plasma. You talked about the impracticality of doing randomized trials of convalescent plasma because the product (plasma) is variable. This doesn’t make sense as a barrier to doing a randomized trial. The point of a randomized trial is to test the treatment that will actually be used in people to find out what the effect of the actual treatment is. If the treatment to be used in people will be variable then we need to test the variable product! 

The key principles that Arturo talked about are to get high-quality plasma and standardize it as much as possible by making sure the plasma comes from people who recovered from the actual disease and have high antibody titers. (And give it early in the course of illness.) None of these are barriers to a randomized controlled trial if it is done well. 

Scientists do randomized trials of variable treatments all the time. You standardize as much as possible but if you are trying to learn the reality of a treatment in practice then you need to test the variation in application. In fact for many treatments the study is based on “intention to treat” analysis instead of “treatment on the treated”. That accounts for people who don’t fully follow instructions which is common in real world application (consider a diet study or a study of talk therapy for example which will have some variability from therapist to therapist). What we really need to learn is how the treatment plays out when recommended in real life, not the theoretically perfect trial conditions. 

Now Arturo’s argument that randomized trial isn’t needed in an emergency situation is an entirely different argument than arguing that the variability of plasma is a barrier. A poorly conducted trial (like many early plasma trials) is worse than no trial at all, but the answer is to conduct good trials, not to reject trials entirely. If the real world treatment is to use local plasma from recent cases then we need to do a trial of the real world therapy process to really understand how it works. 

I’m concerned that you are misleading listeners by focusing on the (false) barrier of plasma variability instead of the (true) barriers of conducting good randomized trials in emergency situations. 

Thanks for your ongoing work in science communication. 


Washington, DC

Sean writes:

Dear TWiVers,

On foot of your episode on the use of convalescent plasma in Covid-19 patients, and the controversy surrounding the absence of RCTs to legitimise same, I was reminded of this article from almost 20 years ago in the British Medical Journal: 

If you haven’t come across it before, then I suspect it may elicit a wry smile from most of your team. Here’s the conclusion from the Abstract:

Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

Love the show!

Best wishes,



Dr Seán L’Estrange
School of Sociology
University College Dublin

Joyce writes:

Hello, TWIV friends,

I was catching up on episodes this evening and just heard you mention on Episode 739 the Pfizer study for adolescents 12-15 and the Moderna study for children ages 12-17 (TeenCOVE). Alan suggested that Moderna had enrolled younger children before the older child/teen cohort, but he may be thinking of another vaccine. Moderna finished enrolling TeenCOVE participants 25 February and began enrolling the younger children (for KidCOVE) soon after.

Rich seemed to question how Pfizer could determine 100% efficacy in their vaccine after only nineteen COVID-19 cases. Interestingly, those nineteen cases (.8% of n=2260) are twice the relative number of cases that Pfizer used to determine the vaccine’s efficacy in adults (.4%).

My twins are in the TeenCOVE study. We felt very confident about participating after spending this past year with you on the podcast. The study is combined Phase 2/3, n=3000, with 2:1 odds of receiving the vaccine over placebo. Vaccine efficacy is listed as a secondary outcome measure. Antibody levels are being monitored regularly, and we are to report to the study doctor if my children develop any symptoms of COVID-19 during the 13-month study.

As they are 16 and now eligible to receive the Pfizer vaccine here in Texas, my children want to be unblinded at their next clinical visit. I’m sure they will not be the first age 16+ study participants to ask about this since other states are also lowering their vaccine age restrictions. Both serious about their role in the study, my children spent days fretting about this. But they are yearning to see their grandparents and move about their world, small and cautious as it may be right now, with just a little more ease.

From their reactions we think my children both received the Moderna vaccine, and hope they can stay in the study, like in the adult version of this trial, to continue to provide antibody and efficacy data over the next several months. This was a difficult, weird winter, but we have been heartened by all that has been accomplished and learned in the past year. Thank you for helping us process and understand it all.

We’ve got 84% humidity at 73*F/23*C in Houston, Texas, and my neighbors are keeping me up,

– J.

Randall writes:


The TWIV podcast just got another recommendation, this time from Shane Harris on the “Rational Security” podcast. 

“Rational Security” deals mostly with national security issues, and Shane Harris is a reporter for the Washington Post. 

The plug begins at 43:15 in the podcast.


Anne writes:

Hey Prof. Raccaniello,

Thought you would appreciate hearing TWiV get a shout-out on this podcast, by Shane Harris, respected national security journalist who writes for the Washington Post, and one of the participants to this podcast, which provides trenchant analysis of national security issues.  Ben Wittes (of the Brookings Institute Lawfare podcast and numerous writings, who also coined “malevolence tempered by incompetence” after the Muslim travel ban was put in place by the previous administration, see < >), also chimes in about the excellence of TWiV.  

Of further interest (especially since I heard you and the team referring to the fact that listener numbers have dropped now that the coronavirus isn’t being discussed as much) is Shane pointing out how much he has learned from TWiV about viruses, and how he plans to continue listening.

If you listen to the last 5 minutes of the episode, you’ll hear his comments about TWiV.

Have a great day,


P.S.  Last week the Rational Security team (Shane, Bem Wittes, Tamara Coffman Wittes; Susan Hennessy was out) discussed the WHO report on the origins of SARS-COV-2 virus.  I have to say it was the best non-scientific explanation of the conclusions of the report, dispelling the notion in non-scientific terms about the possibility of the virus having resulted from a lab escape.  It starts at about minute 36, if you/your team are interested.  < >

Jake writes:

This week’s Left Right and Center episode, a political discussion podcast from KCRW in LA, features Rebecca Lee Smith, Prof of Epidemiology at University of Illinois Urbana-Champaign, talking about the university’s successful implementation of regular COVID testing via saliva collection. I was glad to see a real epidemiologist getting air time! Maybe she could be a guest on TWiV as well?



Ryan writes:

Dear Twiv every time I hear of you doing non COVID-19 news on Twiv, I think of the the pre-Sars-COV-2 era and when the show was meant for biology majors. I will stay  a fan of Twiv and it’s spinoffs given that I have listened to this show since 2018.