Dear Professors TWIV,
Greetings from DC, where it is currently 35°F/2°C and the winds have quieted down to a mere 3 mph after having been ten times that for most of the last 24 hours. I have been slowly catching up on TWIV since falling a few weeks behind while moving house, which meant I missed the last couple of contests. I am sure my wife would prefer I win a Kindle edition rather than get yet another paper book, but you can’t replace the physical presence of the real thing.
Since pedantry has come up quite a bit in the last month or so, I’d like to contribute some of my own, if I may: while the adjective “pedantic” has the stress on the second syllable, the noun “pedant” (of which I am one) has the stress on the first. 🙂
Finally, a listener pick: https://youarenotsosmart.com/2017/02/11/yanss-095-how-to-fight-back-against-the-backfire-effect/
This podcast is the third in a three part series about the backfire effect, or how trying to correct your crazy uncle’s mistaken notions can actually make him believe them more. I’d recommend the whole series (really, the whole podcast), but this episode offers some practical advice that should be useful when issues like climate change and vaccines come up.
See you at the march on April 22!
Hello twiv team!
I’m writing because I’ve been frantically trying to catch up on Twiv (and Twim), and I’m up to Twiv 427. I understand how science and politics are linked, especially for those working for the NIH or related government offices and on government-funded research, but I personally am sick of hearing about politics on the show. I understand that many people are unhappy with the current administration, but at this point there’s very little we as citizens can do. Protests, marches, and contacting our representatives are well and good and can help voices be heard, but ultimately it does not change who the president is and how he runs his administration. I’m frustrated being more than half an hour into an episode with very little actual science even mentioned. I come for virology, not a political discussion.
I can only hope that you’ve backed off on the politics on more recent episodes, because it’s very difficult to fast-forward through the podcast while driving, which is my primary listening time. Please focus on the great science you’re so good at podcasting and leave the political discussions for another platform (or another podcast).
From a chilly night at -2C/29F in Boulder, CO,
Dear TWiV podcasters,
I am a new and avid listener, recently introduced to the podcast by my new friend Rich Condit. I sit with the local meditation group here near Austin and was very happy to meet Rich and his wife, Ibby. I’m a general pediatrician, but my interest in TWiV stems from my undergraduate background in microbiology. As I write this email, it is 25 degrees with a humidity level that can only be characterized as “soupy”. This does not bode well for summer.
I was surprised and honored that Rich chose my blog as his pick of the week since it deviates from your usual science-related theme and Dravet syndrome isn’t even an infectious disease. I am immensely grateful for the kind words and support.
Dravet syndrome is relatively rare disorder – incidence is estimated between 1:20k-40k – and few people who aren’t directly affected by it have heard of it. It is generally described as a “catastrophic epilepsy syndrome” in the literature, primarily due to the refractory nature of the seizures. The clinical syndrome was first described in 1978 by French neurologist, Charlotte Dravet (pronounced Dra-vay), who trained with Henri Gastaut, of Lennox-Gastaut syndrome fame. The causative mutation was not discovered until 2001 by Claes, et al in Belgium. Most cases are caused by a mutation of the SCN1A gene which codes for the neuronal sodium ion channel; over 600 disease associated mutations within the gene have been identified; 40% are truncating and the remainder are splice-site and missense mutations. A few patients with whole gene deletions have been reported.
In terms of possible gene therapy: There was some interest in enhancing the ability of aminoglycosides to suppress premature stop codons in patients with nonsense mutations. I’m not sure what became of that. The only Dravet specific gene therapy research I could find comes from Jane Hsiao’s lab where they are looking at using novel long non-coding RNA to upregulate expression of SCN1A in patients with truncation mutations and haploinsufficiency. I’ve included a link to the article below. As it happens, Dr. Hsiao’s grandson has Dravet syndrome. There is also hope that the new CRISPR technology could be beneficial to Dravet patients.
I was hoping to add some information that would link Dravet syndrome to virology to make it more relevant to your listeners. I recall reading something that indicated that children with sodium ion channel mutations are more susceptible to influenza-related encephalitis, but could not find the article. Acute encephalopathy following acute febrile illness has been reported in Dravet patients and it is recognized that children with any neurologic disease, including epilepsy, are more likely to die from influenza than the general population. We make sure that my daughter, Sarah, and all of her care givers receive the flu vaccine every year.
I do have an unrelated request. We’re still seeing plenty of babies in the office with respiratory syncytial virus. I am curious about any progress, or lack thereof, in developing an RSV vaccine. I trained during the early days of RSV IVIG (RespiGam) therapy and witnessed the development of palivisumab, which is helpful for preemies and other high risk infants, but is cost-prohibitive for the general population. A TWiV episode on this topic would be welcome. I’m certain my colleagues would tune-in as well.
Thanks again for including my blog and for developing an outstanding podcast.
All the best,
Rich and TwiVers,
I was late listening to this week’s TWiV, and I hope I get this follow up email to you in time for Episode 431. As a person with ME/CFS, I want to thank Rich for his message of compassion on last week’s show. I think all of you are sensitive to the suffering caused by diseases, while also geeking out on the science.
Like Angela, the woman Rich mentioned, I have found Buddhist practices to be very helpful in dealing with my personal experience of disease and disability. I discovered many of those practices through the book How To Be Sick by Toni Bernhard. Toni (I am lucky to call her friend) seamlessly weaves her own disease experiences with Buddhist practices, and it’s helpful for any difficulties in life not just disease.
I look forward to reading Angela’s blog, and perhaps Rich or others would find value in Toni’s book.
Steve Bachenheimer writes:
If you teach virology to medical, dental or graduate students, or have occasion to defend the importance of vaccines, you’ll want to listen to this Podcast from “The 1A” (the successor to the Diane Rhem Show on NPR):
It’s an interview and discussion with Meredith Wadman about her new book “The Vaccine Race”, which focuses on the history and personalities involved in the development of the Rubella vaccine. In her book, she also covers the ethics, politics and economics of vaccine development. Towards the end of the hour she discusses the issues surrounding vaccine skeptics. A very lively, lucid and knowledgeable presentation of virology and history of virus vaccines.
I was listening to the show and was happy to hear researcher Nisha Duggal was a former APHL fellow. There was a comment that the funding for the program had dried up, and while it is true the exact fellowship Nisha participated in is no longer around, we do have several other fellowships, including a new similar Infectious Disease Laboratory Fellowship. Unfortunately, this year’s application deadline has just passed, but if any listeners are interested in public health laboratory fellowships, more information is available at aphl.org/fellowships.
MELISSA WARREN, MS| Senior Specialist, Influenza Program
Association of Public Health Laboratories | Analysis. Answers. Action.
Silver Spring, MD
Thanks for discussing my question about the existence of viruses that require more than one host to complete their replication cycles on TWIV 426. I’ve been stuck on this idea lately, and the more I think about it, the more likely it seems to me that viruses like this could exist.
I won’t be offended if you decide to ignore the rest of this long and rambling email, as it quite probably sounds like speculative nonsense, but here is a hypothetical example that I found fun to think about.
Imagine an aquatic phage-like DNA virus that exists in a world full of bacterial cells and bacteria-eating unicellular eukaryotic life forms like amoebae. The virus is able to bind to and enter certain bacterial cells, but not the amoebae (perhaps due to a lack of a suitable receptor on the eukaryotic cell surface). It infects a bacterial cell and integrates to form a lysogen. At this stage perhaps the viral genome is partially expressed through the production of viral mRNAs and some viral peptides, but the virus is still not capable of initiating a lytic cycle (perhaps because its bacterial host lacks the proper post-translational mechanisms to make all the viral proteins functional). In order to produce new infectious particles, the lysogen carrying the provirus and assorted viral mRNAs and pre-processed bits needs to be engulfed and digested by its ‘definitive’ amoeba host. When the bacterial host is digested, its genome, along with the provirus, viral mRNAs, and other bits and pieces enter the cytoplasm of the new, eukaryotic host, where all the necessary machinery is present for translation of the viral mRNAs and complete processing of the viral peptides. This leads to import of the viral genome into the nucleus, and initiates a lytic cycle leading to the production of infectious viral particles. These virions are then released into the environment, where they can infect new bacterial intermediate host cells.
This is purely hypothetical of course, but it doesn’t seem so fanciful. One could imagine that a virus like this could evolve by recombination of genetic material from a bacteriophage and an amoeba virus. Such mixing of viral genetic material might occur when an amoeba infected with a latent virus eats a bacteria infected with a temperate phage. You could argue that a virus like this would have a hard time persisting as a partially expressed provirus in its bacterial host, because the production of viral mRNAs and peptides would impose a metabolic cost on the bacterium that would be selected against during growth of the bacterial cells. That problem could be circumvented if the virus had something to offer the bacteria that conferred a selective advantage. We already know that this is the case with many phage-bacteria relationships.
If one were to compare this example to the life cycle of a parasitic worm like the beef tapeworm, the provirus stage in the intermediate bacterial host would be sort of analogous to the cyst stage of the worm in the cow, while the replicating stage in the amoeba is roughly analogous to the adult stage of the worm in a human host. Just as the human gets infected with the tapeworm by eating undercooked beef, the amoeba gets infected with the virus by eating the undercooked bacteria. Multiple lineages of parasitic eukaryotes have figured this kind of thing out, so why not viruses too? At the risk of offending Dickson, I’d suggest that viruses, by virtue of their rapid rates of evolution, are even better than eukaryotic parasites at finding ways to replicate in all kinds of seemingly obscure niches.
It’s possible to imagine other cycles involving cells that harbour endosymbionts or parasites like Rickettsia, where viruses of the endosymbiont would need to enter a eukaryotic cell first and potentially be uncoated or otherwise modified before they were capable of infecting the bacterial cell. Maybe further study of the WO phages of Wolbachia with their mysterious eukaryotic associated genes will reveal some kind of obligatory processing of the viral particles by the eukaryotic host cells?
The real question is how one would go about looking for viruses like this. I suppose you could get some clues by looking for viral sequences that are shared between different types of cells. For WO phage, you could cure host insect cells of their Wolbachia infections with antibiotics, then expose them to filtered or purified WO phage and look for evidence of viral gene expression in the insect cell. You could also use proteomic approaches or even old fashioned radiolabelled virus so that you could track viral proteins and look for evidence of the insect cells processing or modifying the viral structural proteins. None of this would really definitively demonstrate that a virus is obliged to pass through both host cells to complete its replication cycle though. What do you think? Am I barking up the wrong imaginary tree?
Currently 21.3 C and sunny but windy here in Tasmania.
Dear TWIV team,
Thanks for all your hard work! – a colleague recommended your podcast couple of years ago and I listened very sporadically but I recently started following more regularly – and now I am hooked!
I am a pediatrician, in my second year of infectious diseases fellowship, and have recently started a project on parechovirus.. today I just heard your episode on picornavirus, so I felt like I should write to you all! (by the way in Spanish we also have words for plural You: ustedes, vosotros.. )
Hopefully number 17? By listening to your podcast I am adding even more books to my to-read wish list 🙂 now I still need to find the time
I am very interested in tropical diseases, TB, and now recently more and more interested in virus as well, I am learning so much
Weather here in Columbus, Ohio is about 32F, 0C and was snowing as I came in to work, love it
Thanks! happy new year – looking forward to more episodes on picornavirus!
I have been hearing lately more and more academics (including yourselves) talking about funding basic science research for the sake of research, and I am glad this conversation is in the open. I hope this conversation continues and progresses until someone (government, institute, philanthropist) hears it, understands its significance, and adopts it.
For the sake of the discussion, what would (in your point of view) be the best funding structure for basic research?
We (researchers) all want money to exercise our passion in solving problems and answering questions, and we all want it with the least amount of paperwork and regulations so we can concentrate on what is important and have the freedom to follow the question trail. But there is no denying that some academics would take this money for themselves (some way or another), or waste it, rather than work it for the benefit of society. How would you address this?
I am an early career researcher, assumed my position 3 years ago, and as an early career researchers in academia I am greatly affected by the lack of research funding in general (basic or not), at least in my region of the world.
From Jeddah, Saudi Arabia -> with rare great cold (22 degree C) weather these days.
By the way Vincent, several years ago I took both your virology Coursera courses. At one point through one of them you sent an email criticizing a publication that prematurely announced the MERS coronavirus host. I emailed you for greater explanation and you answered back. From my experience (maybe I am just unlucky) many academics will not take the time to answer a simple question. Thank you for being a great and patient science communicator.
Hello! I would love to win the copy of Infections of Leisure. Hope I am #17!
Also, I wanted to send you a personalized Thank You note for the TWIV mug that you sent me a couple weeks ago for entering the limerick contest. I absolutely love it. In fact, I can’t bring myself to use it at all because I can’t stand the thought of forever tainting it with coffee stains! So it is currently sitting on my highest cupboard shelf so I can admire it.
Dear masters of the TWiViverse
I am hoping to be lucky number 17, although I have missed a few episodes over the holidays so have been catching up and fear I may be a bit late!
I listen to all of the TWi… Podcasts on my commute to and from work, and they keep my mind occupied in the dull monotony of motorway traffic!
As you asked about other podcasts, well I listen to Hardcore Histories, which as Vincent says are extremely long, but also great to kill time, as well as The Infinite Monkey Cage, a physics based comedy show, and some other sports podcasts.
A quick question about the picornavirus, is there any possible clinical significance of the receptor not allowing infection? Could it be used to create some kind of treatment, possibly in humans?
Keep up the good work!
I love the show, and I personally think the weather updates etc. Give a much better connection to the hosts, which is why I love the show so much! Also the new pedant arc is brilliant!
Here in England there is freezing fog, about -3 Celsius, and visibility of less than 50 metres, making my commute even longer, (so more TWiV, yay!!)
Hopefully, with a well timed click of the ‘send’ button, this will land as number 17 in your inbox. This seems unlikely, since I’m listening to the episode a bit later than usual, but you can’t win if you don’t play!
I was in attendance for the recording of TWiV #300 in Washington, DC. Unfortunately, I didn’t have a good opportunity to introduce myself, as my girlfriend (now wife) and I had to rush out after the show. I did, however, acquire a memento in the form of a T4 giant microbe. Review of the video shows that it was lobbed my way by Dickson or Rich. Thanks, guys!
As for the ‘unsolved mysteries’ of biology, my favorites are genes and proteins of unknown function (particularly the ‘dark matter’ of giant viruses) and the prediction of protein structure.
Anyways, heaps of praise for the wonderful TWiX. You are all great company on my commute.
Hi there folks,
I have not heard you talk about this and since it appears to be a pretty big advance in HIV, I would have thought you would have covered it, if you knew about it. I do not have a link to the paper, but here is a link to a story about it. I hope you can cover this and let us know if this is real or just another over blown science story.
I also wanted to go back to the last note I wrote about storage tech. Alan worries about this stuff and I noted that YouTube converted all their videos, and Alan said they had more money than gawd, which should not be hard since (s)he has no money or anything. lol
I would ask that Alan go to the wayback machine at Archive.org. They are trying to save copies of every web site and doing a very good job of it and they convert things to newer formats as needed. I am not saying that we should worry about it, but I think using it to obsess over is not realistic.
Enough from me, here is the link to that HIV story: http://www.medicaldaily.com/hiv-cure-research-2017-successful-antibody-trial-brings-us-closer-destroying-408781
Original paper: Antibody 10-1074 suppresses viremia in HIV-1-infected individuals Nature Medicine
Near the end of TWiV 423, Dickson recommended water from melting snowbanks for thirsty fly fishers. Not so fast. Some algae grow on snow in the spring that can mess up your gut.
Don’t ask for how I know this in detail, but let’s say that spring snow camping in a wilderness can become very unpleasant with a malfunctioning gut.
Hi twiv team,
I’ve been enjoying your show for a little bit now, although I’ll admit many of the other listeners probably have been listening for longer, nevertheless, I’ve been really excited in listening to you discuss various things currently happening in virology. It certainly makes the bus trip to my university, where I’m studying as an undergrad in Microbiology and Immunology, more interesting.
Although I’m hoping to be the lucky writer and enter the contest, I was also hoping you might answer a question that occurred to me while listening to your show.
My question is about prions, discussed most recently on episode 426, everything I hear about the diseases that result from prions are neurological in nature. Why is this the case? Is there something unique or more common to proteins in neurons that make them more likely to misfold and become prions, than proteins in other tissues?
Thanks, and keep up the wonderful work,
I’m writing this from Trenton, NJ on a sunny but seasonably chilly 37°C. Thank you for such an enjoyable podcast for a microbiology graduate to listen to and stay up to date on some of the latest research going on in the world of virology. On the last episode you spoke about the Science March in the Washington D.C., which had me extremely excited. It’s good to see the word spreading so quickly and thank you for helping to continue that. Science should never be muted. Hopefully people wrote in hastily this time and there is a chance this will be the 27th entry, but if not, hopefully we will be united in the Capitol this spring.