Susan writes:
Dear Vincent
Re: the SARS-2 spike/OC43; it should be called a chimeric virus, not a pseudovirus.
Pseudotypes or pseudoviruses are not infectious and cannot replicate. They carry spike/entry proteins from the virus of interest (CoV or other) and are useful for entry and neutralization assays. Pseudovirus particles are assembled by expressing partial genomes of lentivirus or VSV with a luciferase gene or other readout from plasmids along with a plasmid expressing the desired spike protein.
Re: temperature, common cold Coronaviruses such as OC43, 229E and NL63 replicate better at lower temperatures (33 vs 37). We showed recently (Otter et al., PNAS 121 (21) e2402540121, 2024), for 229E and NL63 that this is due to increased innate immune response (IFN etc) at higher temp. This may contribute to why the cold viruses replicate for the most part in the upper respiratory tract and do not progress into the lung. Interestingly in primary nasal cells SARS-CoV-2 replicates equally at 37C and 33C but at late times post infection when innate immune response kicks in, SARS-CoV-2 replicates better at 33. MERS-CoV has no preference for temperature and replicates well in the lower respiratory tract.
(This temp dependence of IFN response was shown previously by Ellen Foxman for rhinovirus)
Susan
Susan R. Weiss
Professor and Vice Chair, Department of Microbiology
Co-Director, Penn Center for Research on Coronaviruses and Other Emerging Pathogens
Perelman School of Medicine
University of Pennsylvania
Steve writes:
Quite enjoyed the recent podcast TWiV 1121 brilliantly rebutting the recent New York Times Op-Ed piece by Alina Chan. Sadly her piece was very likely read by far more people on the Upper West Side and Park Slope, than those who listen to TWiV (sorry). As a result a great deal of doubt and mis-information was spread to “thought leaders” via the Times which will take a long time to rectify (haven’t seen any Op-Ed rebuttal in the Times yet). Nevertheless I applaud your efforts in promoting a fact-based approach to all issues virological!
Steven Bachenheimer
Carrboro NC
Pierina writes:
Dear TWiV Team,
I am currently taking Bi115 at Caltech and have been following your podcasts with great interest. Thank you for your dedication to spreading recent advances in virology! I have a few questions on recent episodes that I hope you can address:
Gene Editing Latent Herpes (TWiV 1119):
Regarding the paper on “Gene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo,” I am curious about the broader impact of the meganuclease therapy in neurons and other cell types. How does the disruption of HSV genes by meganucleases influence overall cellular gene expression and function?
I am also intrigued by the potential cellular responses and long-term stability of the therapy. Are there known adaptive mechanisms that chromatin undertakes in response to disruptions induced by gene editing therapies?
General Questions:
How do you envision the field of gene therapy in the next 10 years? Do you think we will overcome the barrier of immunogenicity? What aspects of immunogenicity studies need to be addressed to draw more significant conclusions about the effects of gene therapies on our immune system?
Clinical Update with Dr. Daniel Griffin (TWiV 1118):
Here I just want to comment on the discussion about long COVID studies. Given the significant differences in symptom burden, immunological profiles, and hormonal levels between men and women with long COVID, I consider sex-specific clinical trials are crucial, and as you mentioned, integrating laboratory tests over self-reports can enhance accuracy and effectiveness by providing objective data for more specific therapies.
Many thanks,
Pierina
Suellen writes:
Vincent and all the other TWIX hosts:
You know me — I’m your loyal listener in Roswell, Georgia who sends a little bit of money to Microbe TV every month. I’ve been listening since the early days of TWIV, and I now listen to every one of your ever-expanding “podcast empire.” I feel like I know all of you, especially the TWIV hosts, and I look forward to every episode, and really enjoy when you go off-piste to talk about gardening, deer in the yard, airplanes, and of course I look forward to the weather updates at the beginning of every episode.
In the latest episode (I think it was 1133), you once again took flak for daring to have an opinion on some of the political issues surrounding science — gain of function, lab leaks, vaccines, etc.
I wanted to write to let you know that, in the opinion of this non-professional-scientist listener (I was an Oracle database administrator for many years, and now I am retired and hanging out with my horses and other horse people), we need you to continue to counter the miasma of anti-think. Without TWIV, I would not know what “gain of function” even is, and I’d probably be reading the editorials I keep coming across that tell me gain of function is dangerous and needs to be stopped, and I’d believe those editorials, because they are written by “educated experts” like Marc Lipschitz. Without TWIV, I’d have to Google “gain of function” to find out what it is — and, in fact, I just did that, and here is the very top entry that popped up:
For those unfamiliar with gain-of-function research, it essentially means juicing up naturally occurring animal viruses in a lab to make them more infectious among humans. This practice is nothing new. Scientists in the United States have long known how to mutate animal viruses to infect humans.
Anyone reading that would think, “This is crazy! We definitely need to stop this kind of research!” But I know from TWIV that this “definition” is not the real story. And I’m able to explain to other non-scientists why this is not the whole story.
Without TWIV, I could not do that, nor could I respond to people who think COVID started in a lab and the pandemic was caused by a “lab leak” where COVID escaped from the Wuhan Lab.
The whole idea behind TWIV and its sister podcasts is to bring science to the people, and that means you do have to discuss the real science behind some of the things that have turned into political talking points. I, personally, benefit enormously from those discussions, and I don’t want you to muzzle yourselves because you might lose a few listeners.
Yeah, of course no one wants to listen to a podcast host raving about politics, but you don’t really do that (not much, anyway!) Mostly, you give people like me, who don’t work in science every day, the knowledge to not only understand the scientific truth behind the subjects I hear about every day on the news. And I almost NEVER hear your side of the argument on the news! Even the NY Times is failing me now. I would cancel my subscription, but I love the puzzles, so I just don’t read the paper any more.
The fact is that there are real, tangible threats to science out there, and someone needs to counter that. TWIV and the other podcasts have been doing that for years, and I don’t want you to stop.
Also, just as an aside: You probably don’t even realize how much you have raised the “Science IQ” of your listeners. I would not even know who people like Dr. Paul Offit were without TWIV. I knew a lot about Dr. Tony Fauci before COVID was even a thing because of TWIV — and I respected him because you all respected him. This is an extremely valuable service that you provide, and I’m not sure you realize it because you know all the top people in your field. But I need to know who’s telling me the true story, and who has a political axe to grind, and TWIV helps me do that.
Sorry to go on so long, but I’ve been ruminating over this for some time, and felt I had to get it out of me. 🙂
I love all your podcasts, I recommend them to people all the time, and, honestly, if TWIV had been around when I graduated from UConn in 1981 with my B.A. in Biology, I might have gone to graduate school and gotten my PhD in neuroscience, which was my plan at the time. But I didn’t really know what I’d DO with that advanced degree, and my advisor told me I’d just end up teaching Intro Biology, so I abandoned my plan and pivoted to the IT field. Now I use TWIV as my tool to help “infect” young people with the love of science. So keep on keeping on!
Suellen
Listener, supporter, and TWiX evangelist in Roswell, GA
Weather: ugh. was up in the 90’s, and now for a week it’s been sticky and raining and in the mid-80’s. All the horses at our barn have either rain rot or hoof abscesses (well, not all, but many). Ask Dr. Mingarelli to explain rain rot and abscesses (hey, I can teach you guys, too!)
Charles writes:
Hello TWiVers;
85 F, 29 C in Chapel Hill, NC, with rain in the area.
These comments are about the Supreme Court’s Chevron and mifepristone decisions.
The courts should be involved with matters of law, but have very limited roles in determining what is good science.
Taking the mifepristone decision as an example. The federal judge, Matthew Kacsmaryk, overruled the FDA and sided with the Alliance for Hippocratic Medicine and ordered mifepristone off the market. This was an absurd power grab by a judge driven by his religion instead of the law. On appeal to the Fifth Circuit, the ruling was softed, but not overturned. On appeal to the Supreme Court, the court did what courts should do, ruled on the law. Kacsmaryk was overruled 9-0, not on science, but on law. The court determined that the Alliance for Hippocratic Medicine did not have standing and therefore could not bring the case to court. You can argue that the Supreme Court sidestepped the real issue, but they ruled on the issue that Kacsmaryk should have. That is our system. I would bet that the anti abortion people are looking for someone with standing to bring the case back to life.
The Chevron decision is a power grab by the Supreme Court and yet another example of them ignoring stare decisis and overturning precedent. Sometimes overturning precedent is a good thing, such as Brown v. Board of Education overturning Plessy v. Ferguson (“separate but equal”). In the case of Roe, it overturned a 7-2 decision that had stood for about 50 years. With Chevron they overturned a 6-0-3 (3 abstaining) decision that was 40 years old.
Congress has had 40 years to fix the Chevron decision if they did not agree with it. To expect congress to be able to write specific laws on scientific matters or for the courts to decide scientific matters is a boondoggle waiting to happen. As neither Congress or the courts have the expertise to understand a lot of the science that goes into rule making. That expertise exists in the EPA, FDA, USDA and other agencies.
There is a way to fix part of this problem. Allow the courts to rule on matters of law, such as in the mifepristone decision. But when it comes to needing expertise, go back to the Chevron decision with one small exception. If the court is convinced that the agency got the science wrong, the court could order the agency to review the data. Nothing more. No bans or restrictions.
Here is the primary holding from the Chevron decision:
A government agency must conform to any clear legislative statements when interpreting and applying a law, but courts will give the agency deference in ambiguous situations as long as its interpretation is reasonable.
Thanks,
Charles
Charles writes:
Hello TWiVers;
A couple of book picks inspired by TWiV 1133. I really hope that Alan Dove connects with both.
The first is Lila: An Inquiry into Morals by Robert M. Pirsig (09/06/1928 – 04/24/2017). His more popular book was Zen and the Art of Motorcycle Maintenance. This book was very popular with people my age. Dr. Dove and the other young members of the TWiV team may be too young to know this author. As with Zen, this book is about a couple of overlapping trips. This one on a boat trip down the east coast. If you do not know about Zen and the Art of Motorcycle Maintenance, read it first.
The second is: My Beloved Monster: Masha, the Half-wild Rescue Cat Who Rescued Me
by Caleb Carr (08/02/1955 – 05/23/2024). Not like his other books, such as The Alienist. It is a book about his relationship with his last cat. If you dislike anthropomorphizing a cat, skip this book.
It has been awhile since I read Lila. I hope my memory is not faulty. Monster was an audiobook that I finished just a few months ago. I recommend it to everybody, but especially to cat slaves.
Thanks,
Charles