TWiV 274 letters

Timothy Sheahan writes:

Dear TWIV,

Wow. You reviewed our paper on your show! Thank you! Dickson was right! I was yelling at my iPhone as I listened but it had to be a very soft yell as my wife was sleeping next to me. HA! You asked many excellent questions during the podcast, I thought I’d try to answer them here. The backstory to the paper is complicated…

Yes…This paper is huge and it took a long time to come out. I’m a molecular virologist and had to learn laser capture, RNA amplification, microarray and the bioinformatics as the project developed. Even though I’d rather be plaque-ing, the science has forced me to wear many hats. Additionally, the fetal livers that we purchase have a random IL28B genotype. Thus, in order to obtain a large enough number of each genotype, we obtained lots of livers over a 2+ year period, rapidly genotyped the cells and only performed microarray on the genotypes that we needed to finish out the work. Dickson brought up the potential use of primary adult hepatocytes. These cells are very finicky, hard to come by for free and if purchased very expensive (~$800 for 5 million cells). They also do not divide in culture (i.e. what you buy is what you have to work with) and normally have to be co-cultured with a non-parenchymal cell to maintain hepatocyte function for longer periods of time. Nevertheless, these are experiments will be done in the future so stay tuned.

Kathy asked about the nature of the HCV-dependent fluorescent reporter and Vincent was correct. The reporter is a fusion of the C-terminus of IPS-1 (aka MAVS etc.) targeted by HCV coupled with a nuclear localized RFP. After cleavage by the viral protease on the surface of cytoplasmic organelles like mitochondria, the RFP portion is free to traffic to the nucleus. Rich also was unclear about the nature of the “mock” samples. Mock cells were transduced with the lentivirus expressing the reporter. We did microarrays comparing primary hepatocytes expressing the reporter to lenti-naive hepatocytes and didn’t see much difference in their transcriptomes and nothing really in innate immunity. This doesn’t mean that things are not happening below the limit of our detection. Unfortunately, we are currently stuck with the reporter in order to carry out these studies and try to address it’s use with lots of controls.

I’ve got lots of great visuals and movies to explain this technique. FYI. If you have any more questions, please don’t hesitate to ask.

Thanks again for discussion our paper. It was great to hear people from outside of the HCV community enthusiastically discuss our work. Virology is awesome right? It doesn’t matter what color it might be.


Stephen writes:

Savanah asked about science writing:

> I am an English Writing major with minors in Applied Statistics and Biology, as I want to pursue a career in Science Writing, or “translating” lab jargon into layman’s English to appear in media such as National Geographic, the New York Times, TWiV, etc.

She might like to listen to TWiV 200, in which you discussed alternative careers for scientists. Also TWiV 210, in which you read my e-mail recommending the UCSC Science writing program. I also mentioned that there are many other excellent graduate science writing programs.

In general, a search in TWiV for “science writing” provides several other mentions.

Stephen writes:

In TWiV 273, you read Bill’s letter about so-called “failed” experiments. “This leads to a waste of mind power and $$, and it is very much to be avoided,” he wrote.

I think there’s an interesting fundamental issue here about received wisdom of what doesn’t work.

In an example I just heard about on the Canadian radio show Quirks and Quarks, Svante Paabo discussed his idea that he might be able to get some DNA sequence from the bones of Neanderthals, etc. Getting DNA from dead tissue had been tried, and it didn’t work. Everyone knew that DNA broke down quickly after tissue death.

But instead of accepting the received wisdom and moving on, he bought a piece of liver from a grocery store, completely dried it in a lab drying oven and recovered DNA. The rest, as they say, is history.

That’s not to say that no ideas can be rejected. Perpetual motion comes to mind. But just because someone tried something once and failed, or even tried it with the best technique and technology of the time and failed, doesn’t mean it’s a waste to try again.

Alice writes:

Dr Racaniello (Vince) -

Please, please, please share your perspective on the cases in California. You are the expert who’s opinion I’m most curious to hear.

Thanks for all you do!

Alice Sato, MD PhD

David writes:

This has been making the rounds on my newsfeed. There is nobody better to comment on this than the man with the “wall of polio”

Ken writes:

Hi TWIVers:

Just saw this in the news, and don’t remember you guys discussing it before:

Mystery poliolike illness affects as many as 25 children in California

Obviously it is pretty rare (only 25 cases reported over the last few years) and it is apparently not even known if it is a virus, but have any of you heard more details?

Snohomish, WA

Current conditions at
Everett, Snohomish County Airport (KPAE)
Lat: 47.92306°N Lon: 122.2825°W Elev: 604ft.

Lt Rain, Fog
Humidity 96%
Wind Speed NNE 5 MPH
Barometer 30.06 in (1018.2 mb)
Dewpoint 36°F (2°C)
Visibility 4.00 mi
Wind Chill 33°F (1°C)

Yes, it was a cold wet bike ride to work this morning…..

Bjorn writes:


What do you think about this? ?

Clark writes:

Hope you discuss that recent outbreak in California of polio like symptoms which may be enterovirus-68. Seems rather scary. Also are the treatments for polio the same as in the 60’s? My mother-in-law was put in isolated quarantine as a very young child with polio. Outside of the physical damage due to the polio it seemed to have psychological impact from the isolation.

Curt writes:

Hello, TWiV team!

Thanks to your podcasts, I’ve become the go-to guy for information on infectious diseases at home and at work. Recently, people have been telling me about alleged polio outbreaks here in California, attributig the illness to the anti-vaccine movement. While somewhat believable, I’ve been meeting them with doubt, since I couldn’t find any reports on it, CDC, EID, or otherwise. Then, articles like this started cropping up:

Basically, either the journalists or UCSF/Stanford are blaming Enterovirus 68 for acute paralysis in children, even though they’ve only found it in two of the twenty recognized cases. Personally, I don’t buy it, but I was wondering what you guys made of it.

Jason writes:

I was listening to TWIV (from last week i think – 272?), and I’m not sure what you were referencing, but there was a period at the beginning when you were talking about helicopters, which surprised me. I was a CH-53 pilot for the Marines for a long time; there were a lot of knowledgeable people on the show talking about CH-47′s, and 54′s (I loved the reference to Chickenhawk). But for the record, whenever a 47 crashed in Afghanistan/Iraq, they always called me (in a CH-53) to come sling it up, and fly it back home, haha.


Martin writes:

Can you respond to this study?

Andrew writes:

Dear TWiV,

I’ve been cherry-picking episodes from your back catalogue for my commute.

Although I could maybe have suspected from the title (Bunya here, done that [TWiV 221]), I was still pleasantly surprised when a discussion started about one of the papers from our lab that we published in PLoS Pathogens last year (Varela et. al, Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host). One of the subsequent comments was about the transmission dynamics involving the Culicoides midges in the winter.

You seem like interested guys, so I thought I’d point out a subsequent study that I did on my parents’ farm. We found a case early in 2012 and, despite the animals being housed for most of the summer, transmission still occurred. This adds further backing to the fact that European midges behave differently from African midges; previously the rather crude dogma was that competent species of midge tend not to enter buildings.

In case you really are interested, we published this in the Vet Record (, but I also discussed some additional observations in my blog (

Many thanks

Andrew Shaw PhD
Research Associate
MRC-University of Glasgow Centre for Virus Research

Stephen writes:

Dear Hosts of This Week in Vocabulary:

First I’d like to thank you for producing the always enjoyable This Week in Virology. I usually also enjoy This Week in Vocabulary, but I want to chime in after listening to episode 269.

Although I pronounce nuclear like the TWIV team, the idea that the pronunciation “nukular” is stupid just because that’s not how it’s spelled is wrong. Full stop. Just try to pronounce all three syllables in Wednesday, or the first ‘l’ in colonel. The point is that we don’t learn pronunciation from spelling. We usually learn pronunciation from hearing others speak; we have much of our vocabulary before we can read. So people who pronounce the word “nukular” aren’t stupid or bad at figuring out how a word is pronounced from the way it’s spelled.

Pronunciation learned from spelling can lead people astray. Anyone who read a lot as a child probably remembers pronunciations that they got wrong because for years they based their pronunciation on spelling, until they finally heard someone else say the word. This phenomenon, called spelling pronunciation, has actually caused the pronunciation of a number of words to change away from what was once considered correct. Wikipedia includes a list of examples on their spelling pronunciation page

The “nukular” pronunciation isn’t simply a less prestigious pronunciation, however. It’s been with us as long as the nuclear era and is used by some experts in nuclear weapons and power. Apparently some in that industry distinguish “nukular,” referring to atom splitting, from “nuclear” in other contexts (such as the stuff in the cell). Many words have different pronunciations for different meanings. E.g. you can “desert” someone in the “desert.”

I’m not saying you should change your pronunciation, just don’t be so dismissive of people with alternate pronunciations. They came by it honestly.

Thanks for the podcast,

Jon writes:

Cat writes:

Hi TWiV team,

I am pursuing a research career from a very non-traditional background (pharmacy student to business program graduate to working in IT and marketing for the last 8 years). All of the microbiology programs I am applying – quite appropriately – are looking for research experience. I was wondering if you or any of the TWiV gang had any advice to lend as to how to gain research experience for a person such as myself, a 31 year old many years removed from a clinical/research setting.

Thanks in advance for your wise words and for the absolutely amazing content you all provide us – and hopefully for a little TwiV bump!

Warmest regard,

Nickie writes:

Dear TWIV team,

I have been listening to TWIV regularly for about a year or so, and I love the podcast! Thanks for providing this great service.

On TWIV 268, a reader asked about scientifically plausible scenarios for viruses to turn humans to zombies. A while back I was looking for some interesting topics for undergrad non-majors biology when I came across parasites that alter the behavior of their hosts. Below are some links from a Google search that provide examples of these parasites (2 are viruses). These articles are not from the primary literature, but point toward some examples that could be further researched and used as the basis for fiction.

Of late you have featured models of viruses on the show. A couple of summers ago while at Zoo Atlanta, this plant caught my eye. I was drawn to it, and ultimately snapped a couple of pictures, as it immediately made me think of a virus capsid. Although not an entirely accurate model, it is a pretty cool stand in.

Thanks again for the great podcast,


James writes:

Hello Vincent and the TWiV team

It is 7pm local time, 9°C, with a south westerly wind at 26km.h-1, although there is a wee chill in the air I’m still a bit warm, as I still prefer the Scottish climate I was more accustomed to until recently. As I look out from my 17th floor window I can see all the major landmarks across London, so it is pretty clear night considering the recent conditions over this side of the pond.

Just been listening to yet another great TWiV (and a TWiP too), and the team got into a short discussion about your listener’s demographic and Coursera ‘students’, of which I am both and got me to thinking it would be a good time to say ‘thanks’.

Personally I listen for a variety of reasons. Your podcasts and Coursera course is fantastic- especially for me. I’m 28 and a graduate in Marine Science, mainly biological but I tried to keep a good amount of physics and chemistry in there as I am passionate about it all- even the statistics. Having always spent my life looking for challenges [always found school too basic] I needed to maintain a mental stimulation and this usually meant self-education. This continues now, being mentally ‘under-employed’. I listen to your podcasts, along with some other academically minded podcasts, especially at work. Your podcasts are great as some discussion being on a level at which I can miss bits due to work disruptions and still maintain the thread of discussion. While when you progress to the more advanced topics which expand my knowledge (as my detailed disease knowledge largely relates to the bacterial world from my studies and time working on a recombinant vaccine). Although the advancement of ‘open’ publishing, there are still so many paywalls and once you leave academia the subscription access to the larger databases goes too, along with the colleague debate. So what you provide is invaluable.

Meanwhile your Coursera course gives the opportunity for organisation through the subject matter. It could be argued I could largely pick up resources and self-learn as I have many other subjects, but your course streamlines and ensure the topics are approached in a sensible sequence. While your lectures make you feel like you are a part of something still and gives more of a participation feeling.

As for the discussion about partners losing their time together; my wife is even more qualified and even more mentally under-employed, she tends to be at work a lot while I am at home and vice versa. So this works perfectly for us- not sure about the rest of the students.

So keep going- you’re keeping me sane!

Many thanks

from the UK- if you couldn’t tell.

Sandra writes:

Ok this scares me – is the risk exaggerated?:

11 common disinfectants can’t kill HPV

Sandra in Dallas

Timothy writes:

Hi team. Although I’m not a coursera student myself, I have a suggestion for Ashlee when reading her discussion posts online. During the discussion on CCR5 screening and the potential to change people’s behavior regarding sex and intravenous drug use, it was noted that none of the responses were exceedingly open about how it might increase their chances of partaking in more risky behaviors. Some confounding variables were posited regarding the sample pool of those taking an online virology course. Another potential variable is that Ashlee was reading the full names of the respondents on the air. Since topics such as sex and drug use carry significant social baggage, the knowledge that their identity would be tied to the response might bias more conservative answers. Perhaps disclosing only first names or maybe just initials would foster more open and honest answers. Apart from that, I’m really enjoying her segment despite the fact that I’m not involved in the course. She is a natural podcaster – perhaps a future recruit to carry on the TWIV legacy to the next generation?

- Tim

Jenn writes:

Hi TWIV team!

I work at Weill Cornell Medical College as a technician in a tuberculosis lab. Love the show! I enjoy listening to all things twix, while doing my bench work. It’s currently 2C and very slushy from yet another snow storm, Pax. I think it’s been over 12 inches so far.

I wanted to share a picture of an PSA poster I saw on the subway today because of your many discussions on educating the general public on science. I think this had a lot of potential, but fails terribly by not using scientific terminology. Seeing this makes me very frustrated, but you can’t blame the general public for not understanding the difference between a virus and a bacterium when we call them all ‘germs.’ I see this poster and I think why can’t I just take an antibiotic for the flu like other illness caused by germs!


Michael Imperiale writes:


I’d like to nominate this for a listener pick: