Justin writes:

https://www.cnn.com/2020/09/08/health/covid-19-vaccine-pharmaceutical-companies-pledge-bn/index.html good for them bad code the political pressure

It never should have gotten this bad.

Dave writes:

Hello team TWIV

Greetings from north central Florida where have been experiencing what appears to be a SARS-CoV-2 variant. It has been named Virus Ignoramus and it has spread rapidly from the Sheriff (the one who ordered all of his deputies to not wear masks and prohibited the general public from wearing a mask in the sheriff’s office building), to the Mayor of Ocala, Chief of police, City Council, County Commission, State Education Commissioner, State Department of Health, and Governor. It appears that the R-naught of this virus far exceeds the paltry 12-18 of measles and that the transmission of this highly contagious virus appears to only require that the infected open their mouths.

The Moderna candidate vaccine is currently in a large multi-center phase 3 clinical trial that plans to enroll a 15,000 placebo arm and a 15,000 mRNA-1273 candidate arm.

Does anyone care to proffer a  SWAG, Scientific Wild-Ass Guess (2) in response to the following questions.

Approximately how many participants in each arm would have to become infected in order for the results to be statistically significant?  

A large scale multi-center trial affords less bias than two adequate and well-controlled trials (1). About how many of the 89 locations have to yield similar results?

I hope you will not use terms like z score or p value as at my advanced age a z score relates to number of times one has to get out of bed at night as influenced by the second term.

You and the team have a great way of making the complicated appear easy. Keep up the great work.

“I would rather have questions that can’t be answered than answers that can’t be questioned.”

― Richard Feynman



(1)    Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products Guidance for Industry https://www.fda.gov/media/133660/download

  “Large multicenter trials can include a broad range of subjects and investigation sites and have procedures in place to ensure trial quality (e.g., investigation site selection, monitoring, and auditing). They generally are less vulnerable to certain biases such as selection or measurement bias, are often more generalizable to the intended population, and can often be evaluated for internal consistency across subgroups, centers, and multiple endpoints.”

(2) Scientific Wild-Ass Guess (SWAG) is used to describe an estimate derived from a combination of factors including past experience, general impressions, and heuristic or approximate calculations rather than an exhaustive search, proof, or rigorous calculation. The SWAG is an educated guess but is not regarded as the best or most accurate estimate. The SWAG is not computed or proven rigorously, but the proponent asserts his or her own judgement suffices to rationalize the estimate; and it may, in time, be viable to produce a rigorous forecast of increased precision.

Shantel writes:

Knoxville Tennessee was an incredibly humid 88F today. I’m just an artist with my own green cleaning business that gives me plenty of time to listen to all your podcasts while I work. I’ve always had a passion for science and take notes while I listen for further research in my attempt to understand virology. You guys have given me many rabbit holes to explore since I first stumbled upon TWIV back in March.

I’m wondering about what Shane Crotty said about cross reactive memory T cells and how it might relate to a rushed vaccine. If 50% of people have them and the FDA is only requiring 50% efficacy, how will we know if the vaccine is actually helpful? Hope this isn’t a dumb question but it seems like I’m missing something. Thanks so much for all the work and time you guys put into these podcasts. You cannot imagine the joy you bring me. I feel like I missed my calling and am seriously trying to figure out a plan to further my education once this mess is behind us.

Keep it grumpy!


Yegor writes:

Dear Vincent and Friends,

I’m just a COO of a small biotech vaccine company, but I think I can contribute to your discussion about the possibility of SARS-CoV-2 vaccine trials ending in the near future. While fairly unlikely it is indeed possible. Data Safety Monitoring Boards (DSMBs) for clinical trials have regular (and sometimes unscheduled) meetings on which they review various aspects of data being collected during the trial, both the processes for data collection and the data itself. A lot of the analyses they do are quite technical and way over my head, but they do review both safety and efficacy results for study groups and based on that review may recommend early termination of the trial. My understanding is that they initially review the data in a blinded fashion (Group A vs Group B), but they also have the ability (if needed) to immediately unblind the study and see which group is placebo and which is the treatment.

Why can they recommend stopping the trial? Many reasons, but some of the most obvious ones:

  • They may find that treatment is obviously causing harm with a lot of adverse events, making it unethical to continue administering the treatment
  • They may find that treatment is obviously ineffective or that it’s not effective enough to allow the study to reach its primary objective
  • They may find that treatment is so clearly effective and so much better than placebo that it would be unethical to withhold the treatment from the placebo group

Any of this can happen even before the trial is fully enrolled if the statistics are convincing enough. Of course, if the trial is properly powered, none of this should happen, it’s always a surprise when it does.

These DSMB reviews are scheduled in advance, so it should be possible to find out when they are happening for the Phase 3 trials that have already started. If any of them are happening between now and November 3rd, we may theoretically have an answer (either positive or negative) before the election date.

I used to listen to you during my long commute. Now I’m working from home, so have less time to listen, while you doubled (or tripled?) your output. Thus, even after ditching some other podcasts from my feed, I can’t keep up and now resorted to switching between listening to the most recent episode and the oldest one I have not yet listened to. Sometimes this gives a very interesting perspective by putting back-to-back some stories that developed over the past month or two.

I consider you an essential resource and am very grateful for having the latest COVID research summarized for me by you and your guests. Thank you!


Yegor Voronin, PhD
Chief Operating Officer
Worcester HIV Vaccine

Tim writes:


I applaud your reader’s suggestion of Tom Nichols’ book – The Death of Expertise.  There are many vectors for this death, but my favorite is when experts pontificate about things in which they are not necessarily experts.  I am constantly reminded of this in my conversations with my wife.

Confirmation Bias is a constant vector as well often brought up by Dr. Griffin when he pushes for evidenced based medicine with anecdotes from expert Drs.

I read Shane Crotty’s Ahead of the Curve based on your recent show and was intrigued by the failing of David Baltimore and John Dingell who sacrificed expert knowledge for belief.  Belief, no matter how heartfelt or data driven is the ultimate vector for Expert death in this world perhaps.  Would that we could all but just read scientific papers and wait for confirming and reassuring replications.

Here is a choice section from Tom’s book – please address if you discuss it.  Note this is a complicated book and not one to be loosely discussed or briefly summarized.  Quotes like the one below are an example of how hard it has become to talk about anything.

Maybe Dickson has a point… Vincent complains too much.  Maybe not… No one is an expert on all things.  In the end I prefer dogs that bark to those that bite.

This is from Chapter 2…


How Conversation Became Exhausting

Thomas M. Nichols

The Death of Expertise: The Campaign against Established Knowledge and Why it Matters

The late science fiction writer and medical doctor Michael Crichton used an example from the early days of the AIDS epidemic in the early 1980s to show how people are so often convinced that they will always draw the shortest straw. The disease was poorly understood at the time, and a friend called Crichton for reassurance. Instead, she ended up nettled at the doctor’s insistence on logic:

I try to explain about risk. Because I have recently noticed how few people really understand the risks they face. I watch people keep guns in their houses, drive without seatbelts, eat artery-clogging French food, and smoke cigarettes, yet they never worry about these things. Instead they worry about AIDS. It’s kind of crazy.

“Ellen. Do you worry about dying in a car crash?”

“No, never.”

“Worry about getting murdered?”


“Well, you’re much more likely to die in a car accident, or be murdered by a stranger, than to get AIDS.”

“Thanks a lot,” Ellen says. She sounds annoyed. “I’m so glad I called you. You’re really reassuring, Michael.”

A decade later, AIDS was better understood and the hysteria faded. In later years, however, new health risks like Ebola, SARS, and other rare afflictions have caused similar irrational reactions, all of them a concern to innumerate Americans who worry more about an exotic disease than about talking on their mobile phones while driving home after having a few drinks at the local pub.

I think Nichols would like to take back this last paragraph.



PS. I am still working through the bibliography of Rules of Contagion.  This is another vector of Expert death where epidemiologists apply R_0 to ideas and belief.  That is another great book you have dropped in my COVID world.  That one is taking me a bit longer to digest… lot of math there.

PPS.  Rich – I am retaking my Calculus series from school and look forward to taking Organic Chemistry.  Would that all aged humans did that… it really is fun to tackle material like that.  I enjoyed that side bar today.

Lisa writes:

Vincent, Brianne, Rich, and Dickson

Right after the See It Can Be Done episode recorded, we got some early numbers.  As I watch the colleges wrestle with their COVID-19 responses, I see both positives and negatives.  Alan mentioned that a lot of the problems seen in the universities were anticipated, and I am as critical as he of the schools sending infected young adults home.  Having a plan to deal with quarantine and isolation at the school is part of a comprehensive plan.

We had some great successes:  since the start of the high schools and colleges that are on the protocols we built with the committees at each institution, not one case of SARS-CoV-2 infection was traced back to the classroom.  Masks, limits to class size, attention to good ventilation, and simple attention to surfaces (no hygiene theatre here) is working.  As are the areas set aside for eating and studying, with the spacing and plexiglass.  Given the space and the opportunity, students are doing the school thing right!

We have also had some “opportunities to learn”:  we learned that some of the collegiate congregate living spread was due to shared vaping devices, and immediately launched a public service announcement and brought in social organizations to support.  We also shared with other colleges ASAP.  We also learned that the fraternities and sororities are holding virtual rush events, with members crowded around a screen without masks.  Same thing.  That pretty much eliminated any benefit to the “virtual” aspect.

Positivity rates at Purdue?  Public knowledge now–we think sharing data is important to help all schools.

Move-in positivity rate:  0.95%

Current 7-day positivity rate:  2.64%

Most common symptoms:  body aches and sore throat

So we are redirecting our attention–public education, peer-to-peer instruction, and fostering the social activities that are low risk.  We additionally have reached out with very specific advice to non-school housing as, although they had policies in place, they needed brushed up a little.

The high schools are in parallel.  We have mostly seen transmission related to parties decrease after the initial burst after graduation.  Athletes have pulled in their bubbles, focusing on fall sports.  And social groups are keeping small.  Surveillance testing has been restructured to test before the week’s practice begins, eliminating the exposure to the whole team. Believe it or not, the team members arrive early on campus, submit their saliva for PCR testing, and results are out by midday. And the numbers here are dropping.  

Current school positivitiy rate:  0.2%

Most common symptom:  body aches.  

Kids with temperatures over 100.4:  1, and his was 100.6.

Having dinner with my girls last night, they offered their thoughts, and what they told me is keeping me going.  They said they wished they could just not know, and just walk around like all the people they see doing whatever they want to do. But they can’t because they know because we teach them, and they can’t be complacent.  We must continue to educate in the schools and the community so these kids can continue to attend in-person school, play sports, and maintain a low risk for infection.  We still believe it can be done.

Have a great week–we look forward to each episode!

Lisa and David

Hugh writes:

Great stuff. Thank you for the extraordinary amount of time you put into this. Finally got around to donating today.

My understanding of the limerick form is that it requires a strict AABBA rhyme scheme, with the 1st, 2nd, and 5th lines being 9-10 syllables; 3 and 4 are 5 syllables. And they are mostly in an anapestic rhythm. Thus:

Ever since this pandemic occurred
Out from our own homes we have been lured
Symptoms are varied
Doctors are harried
This damn virus is one right bastard

And to explicate:

Ev-er since’ this pan-dem’-ic o-ccurred’

Out from our’ own homes we’ have been lured’

Symptoms are varied

Doctors are harried

This damn vir’-rus is one’ right bast-ard’

Some of your contributions sound closer to haiku, the Japanese origin 5-7-5 three liners:

Government choices
Poor black brown deaths more often
Is it genocide

But who cares. I enjoy the light touches and sprinklings of poetry you read out, regardless of how you label them.

Hugh Hill
Assistant Professor, Department of Emergency Medicine
Johns Hopkins University School of Medicine

Matt writes:

TWiV Team,

Thank you for continuing to keep us all up to date on the newest developments – I feel like your team stays a week or two ahead of the headlines and these podcasts remain a great aggregator of current developments and a place of thoughtful discussion.

While we remain a few months out from hitting endpoints on Phase 3 vaccine trials, it looks like we are likely to get to the point where we have multiple approved vaccines. Across the set of vaccine alternatives that are ultimately approved we are likely to see different levels of measured effectiveness, the measures of effectiveness are likely to differ across trials/candidates, and the timing of when each approved candidate becomes broadly available is likely to differ by many months.

While having multiple approved candidates is in many ways a good problem to have, are there any studies that look at the interactivity of successive vaccinations? If the first candidate that is approved and broadly available is only moderately effective (e.g. reduces the incidence of severe disease by 50%), could inoculation with the initial vaccine have any impact on the immune system’s response to a subsequent vaccine that has shown higher trial effectiveness? 

I’ve found some studies showing improved outcomes in successive IPV/OPV inoculations, but unsurprisingly there don’t seem to be many precedents for this sort of thing. I could also see a scenario where a primed immune system shows a less robust response to a second vaccine. If the impact of successive vaccinations across different vaccines is unknown when the first vaccine becomes available, and if that vaccine shows good but not great efficacy, how should people weigh the decision to go with what comes first vs wait and see? How should public health officials draft recommendations when what is best for any individual making these decisions may be different than what is best for society as a whole?



PS- the weather here in Long Island is feeling more fall-like and fishing starting to pick up on the south shore. Should be a great fall!

Tommy writes:

Good morning all,

I’m listening to your morning podcast. It’s that great morning listening. 🙂 Nobody is here at work yet, but I’m already reviewing case investigations. We’re having an outbreak on our university campus, but approximately 75% of cases are off-campus residents and there is no common characteristic besides them being students. With nearly 30,000 students, testing all of the students is extremely difficult. On top of that, they’re having a lot of difficulties with the legality of forcing individuals to a medical test. I just thought you would find this interesting.

Have a great day!