Junio writes:

Could you talk about SFTSV in a future episode of TWiV please? It feels scary to hear that infections reported in residents of Japan who haven’t even visited China.

Matthew writes:

Dear Vincent et al….

I am a TWiV listener from Zambia… or at least I am when I can get the bandwidth. I am a University College London (UCL) post doc settled in Zambia, where I am Programme Director of the UNZA-UCLMS Research & Training Programme (www.unza-uclms.org), a collaborative research and capacity development programme between UCL and the University of Zambia.

I write to inform you about HerpeZ’, a Zambian research organization which I have set up, dedicated to promoting herpesvirus research in Zambia and across sub-Saharan Africa.


UNZA-UCLMS and HerpeZ are based at Zambia’s largest referral centre (roughly 2400 beds), where HIV prevalence among adult inpatients is 70% (paediatrics – 10%, and many more maternally HIV-exposed infants). Mortality rates are extremely high (reaching 40% in NICU) with many patients suffering from complex co-infections associated with HIV. The setting is very interesting with respect to herpesviruses, with HIV-associated and childhood endemic (not-HIV associated) KSHV, as well as universal HCMV and HHV-6A infections in infancy. We currently have some HHV-6 projects ongoing, working with the HHV-6 Foundation, Harvard Med and Fujita Health University but are interested to establish more collaborations, covering all 9 herpesvirus species for whom humans are their natural host. We have two autopsy studies and several retrospective prevalence studies ongoing, and are particularly focussed on trying to establish pathology linked to some herpesvirus infections with a view to future diagnsotic or therapuetic interventions.

If you could give us a mention on TWiV it would be amazing, or simply forwarding this email off to a few of the herpesvirus groups you know at Columbia and elsewhere.

Many thanks,

Matthew Bates, PhD

Programme Director

UNZA-UCLMS Research and Training Programme

Department of Paediatrics and Child Health,

University Teaching Hospital,

Lusaka, Zambia

Robert writes:

To the lady and gentlemen of TWIV,

I have been listening to the podcast since last year and have been preaching the gospel that is TWIV to students and professors equally at the University of Oklahoma, where I am a senior microbiology major. I was listening to your discussions about rabies virus during episode 215 and wanted to add my own input. I had to do some research about this virus last semester for a class I had in virology and wanted to send you the key references I used for the presentation. The first article by Pulmanausahakul et al (J. of Virology 2008) at Thomas Jefferson University compares cell-to-cell spread of attenuated vs. wild-type rabies virus. This article may help explain the difference between the two and how the wild-type virus is able to hide by controlling its replication rate. The other attachment is a Nature reviews article from Schnell et al. at Thomas Jefferson University about the biology of rabies, including what we do not know. I found the review article extremely helpful in understanding the life cycle of the rabies virus.

Love the podcast and the wide range of people that you all reach with your podcast. Keep up the good work.

I attached the articles for your information.

http://jvi.asm.org/content/82/5/2330 and http://www.ncbi.nlm.nih.gov/pubmed/19946287

John writes:

Dear Twivonauts,

Your wonderful podcasts have single-handedly rehabilitated virology, in my eyes. Our medical school virology lectures were so completely forgettable that I could not have said one inspiring thing about the field before discovering TWIV. In fact, the only thing I can even remember about the lectures happened after a classmate asked one of our professors to please put more information into his class handouts. Perhaps emboldened by his recent Nobel Prize, the professor’s next handout contained the entire DNA sequence of the SV40 virus, which, he explained with a straight face, was quite a bit of information indeed. True story.

Although I love TWIV, I find it necessary to dispense a few bits of tough love.

First, did you know that it contributes to global warming? Whenever I travel from San Francisco to Los Angeles, I have to decide whether to drive or fly. Given the need to arrive early at the airport, and the slow shuttle busses going to LAX’s rental-car lots, flying is only about an hour faster than driving. So it’s almost a tie. What tips the balance decisively to driving, however, is that I get five distraction-free hours to catch up on TWIV!

Number two: Each week’s series of weather reports twinges just a bit. Blame it on Arthur C. Clarke’s science fiction novel, “Imperial Earth,” whose 23rd-century hero has lived his entire adult life indoors, in pressurized tunnels dug into Saturn’s moon, Titan. When the hero visits earth for the first time, he is surprised at the whole idea of weather and observes “the amount of Terran conversation devoted to that was quite incredible!” (Chapter 37). So your weather reports always make me think “Typical earthlings.” ūüôā

Number three: May I gently suggest lowering, by just a bit, the threshold for inviting clinicians onto the show? I have, a couple times, squirmed slightly during your discussions of human illness. In the end, you get it almost all correct, but only by hanging on with fingernails.

Finally, and this is the most serious one, in TWIV 210 (or thereabouts), Alan Dove minimized the occupational benefits of knowing how to program computers. I must disagree strongly, on two grounds. First, so long as most people cannot program, those who can will be viewed with some degree of awe by those who cannot. Trust me, this alone can get you far in life — even in the sciences. Second, programming is enormously liberating to the imagination. If I can conceptualize something, and if there is no off-the-shelf software tool that lets me fully express that concept, I can build my own tool to incarnate the concept. It’s like adding colors to a painter’s palette. What artist wouldn’t want that? Only if a job involved zero imagination and already had ideal existing tools would I yield, but such jobs do not exist: a computer would have already replaced the human.

I recommend that beginning programmers learn the Python computer language. It is simple, elegant, and yet enormously capable. It is also free. I use it routinely to stitch other computer tools together into a single seamless system. This is incredibly useful in writing, where, for example, I can generate a complex figure having multiple labels, refer to the labels by name in text documents, typeset all the pieces, assemble the pieces into a finished book or article, and then revise, revise, revise, knowing that the references adapt and don’t break. I could give other examples, but the simple truth is that I can write books that very few people can, only because I can tell a computer unique ways to put medical things on paper. Multimedia opens even bigger possibilities.

May I suggest Python as a user pick of the week?


But really, all glory to you for making virology vibrant. One last thing. I almost got you on network TV. For six seasons I was a medical advisor to the television series “House, MD.” Yes, we stretched facts, but never broke them. Very occasionally, however, we had story constructs allowing the writers to invent diseases. So I was eager to sicken one of Dr. House’s patients with an endogenous retrovirus that somehow became functional. ERVs and parasitic wasps are the two most astonishing things I’ve learned from TWIV. Alas, I couldn’t make the ERVs happen. It would have been an honor to spread your contagious enthusiasm for virology to millions.



Palo Alto, California

Josh writes:

Dear TWiV Doctors,

I saw this article on Reuters about H1N1 Vaccine-associated narcolepsy:


The title of the article is “Evidence grows for narcolepsy link to GSK swine flu shot”. Despite the title, no evidence of any such thing is actually provided. There is no link to any research or publication to back up this claim. The only report about I could find is from September of 2012, so I have no idea what prompted this article.

A paragraph in the article states that:

Independent teams of scientists have published peer-reviewed studies from Sweden, Finland and Ireland showing the risk of developing narcolepsy after the 2009-2010 immunization campaign was between seven and 13 times higher for children who had Pandemrix than for their unvaccinated peers.

There is no reference to who those studies were carried out by, no link to the studies in question and the only “evidence” from those studies included in the article is a graph showing something like an increase in narcolepsy cases in Sweden and Finland.

The article states that 30 million people were given this vaccine and 795 of them developed narcolepsy or a related condition since 2009. The article also says that between 200 and 500 people per million develop this condition every year. That means in three years, between 6000 and 15000 people out of 30 million should develop narcolepsy. It does not say those 795 cases were above the baseline of between 6000 and 15000 people out of 30 million, if that is indeed the baseline.

Also, there were also parts of an interview from Dr. Goran Stiernstedt, who has some public health role in Sweden, that seems to suggest that vaccines may not be worth the risk. That part of the article says:

“The big question is was it worth it? And retrospectively I have to say it was not,” he told Reuters in an interview.

With hindsight, this risk-benefit balance is unacceptable. “This is a medical tragedy,” he said. “Hundreds of young people have had their lives almost destroyed.”

I believe he meant that, only that from a purely mathematically point of view, it didn’t come out in their favor this time. I don’t think he is questioning the logic of public health vaccinations. I emailed Dr. Stiernstedt and asked if he could clarify his comments, but have not yet received a reply.

I found a report about it here, from the European Centre for Disease Prevention and Control (ECDC):


It’s a long report. The conclusions are on page 10. They say that:

The pooled background incidence rate of diagnosed narcolepsy was low and stable at around 1 per 100 000 PY between 2000 and 2010 (0.85/100 000 PY prior to the vaccination campaigns)

Lower background rates of diagnoses were observed among children: <5 years and 5‚Äď19 years (0.12/100 000 PY and 0.56/100 000 PY, respectively

No increased incidence rate of narcolepsy was observed in temporal association with the 2009 pandemic itself.

The overall incidence rates of narcolepsy differed substantially between the signalling and non-signalling countries after the start of the vaccination campaigns: 1.67/100 000 PY vs. 0.95/100 000 PY, respectively.

In the signalling countries the following incidence rate patterns were identified:

In Finland, an increase in the incidence rate of narcolepsy diagnoses after September 2009 was observed in children and adolescents 5‚Äď19 years of age with a relative risk of 6.4 (95%CI 4.2-9.7).

In Sweden, a similar increase was also observed after September 2009 in the 5‚Äď19 year age group with a relative risk of 7.5 (95%CI 5.2‚Äď10.7).

And in conclusion (bottom of page 10 in the pdf)

The observations are sufficiently strong and consistent for children in the signalling countries using different methodologies to warrant further investigations as to a possible mechanism. While it is the case that the vaccine concerned is one with a novel adjuvant there is a confounding factor in Europe in that this was the only vaccine offered for children in any volume in Europe. Hence it cannot be concluded that the adjuvant is the cause of the observation. Equally there is also the possibility that it is the combination of vaccination and influenza transmission or another unrecognised infection or environmental factor in individuals with developing nervous systems. There will be a role also for animal models and mechanistic studies.

The report also has lots of warnings about media attention effects and other problems that might affect the reporting and analysis of data.

I just wanted to put the real information out there, and give people who are concerned a link to actual data. The Reuters article does nothing but scare people about vaccines. The author, Kate Kelland, actually won an award from the EU for health reporting in 2011. The link is here: http://ec.europa.eu/health-eu/journalist_prize/2011/winners/index_en.htm She’s also on Twitter, here: https://twitter.com/kkelland



Robin writes:


Will have to plow through the rest of the of the Virology 101 episodes or risk narcolepsy from the more technical aspects of TWIV. Last had virology in 1967 med school.

Thanks for an addictive set of podcasts from Vince and his three crews.

William writes:

Dear Virologists,

The resumption of transmission studies on avian flu this week has¬†elicited a number of claims in the UK press that the case fatality¬†rate for avian H5 in humans is greater than 50%. You have previously¬†covered the contrary opinion, voiced by Palese and Wang (1), that the¬†seroprevalence of H5 in some Asian populations may be high enough for¬†this case fatality rate to be ‘likely orders of magnitude too high’.¬†Thinking about this today made me wonder to what extent we can rely on¬†seroprevalence as an indication of disease and I’d be interested in¬†your thoughts on this. It strikes me that there’s really a grey area¬†between ‘disease’ and ‘lack of disease’, with asymptomatic infections¬†lying somewhere in the grey area depending on the extent of infection,¬†impact on metabolism, infectivity (in non-zoonotic infections) and so¬†on.

It strikes me that we really need a clearer understanding of the¬†mechanism underlying the H5 seropositivity of Asian populations before¬†we’re in a position to assess its impact on the case fatality ratio,¬†and I don’t see that the ‘likely orders of magnitude too high’ claim¬†is justified. Perhaps a better statement might be ‘Given the limited¬†surveillance, it is not possible to provide an accurate case fatality¬†rate, but the current figure of 50-80% represents an upper bound’. I¬†am less sure how one should respond to a question from a journalist -but I have a feeling that saying ‘it may be that high, but we just¬†don’t know’ is probably better than agreeing with the 50-80% figure or¬†saying that it’s probably far too high.

By the way, at age 54 I am probably one of the oldest science¬†postgraduate students listening to TWIV – I am in the final year of a¬†part-time Bioinformatics PhD at Birkbeck in London. I am lucky to be¬†able to study a subject of great interest to me without too much¬†concern about a future career – at the same time I have chuckled a¬†couple of times when you’ve had questions from people in their¬†thirties asking whether they are ‘too old’ to be a postgraduate¬†student! My advice would be that if you really want to do something¬†that will develop you, and you’re in a position to do it, you should¬†go for it, and let the future work itself out. Certainly the¬†discipline and approach I have gained from my recent studies have been¬†very helpful in my work in mainstream IT. I don’t know what the future¬†holds for me, but I would be sorry to leave the world of research¬†behind.



(1) РPalese P, Wang TT. 2012. H5N1 influenza viruses: Facts, not fear. Proceedings of the National Academy of Sciences of the United States of America (January 25).

Keith writes:

Hi All,

Thanks for a great virology 101 episode of TWiV. You created a great summary of the way that viruses manipulate the cellular machinery to infect cells and reproduce themselves. I have been looking for a way to incorporate these concepts into our molecular biology course to engage students in the deeper exploration of transcription and translation machinery that we do in the course. I think you provide an excellent template with the structure of this episode. Is there any way you could post the slides in a powerpoint or keynote format for easier use in lectures?

I was also writing with a concern about one of the points in the discussion on splicing. When you all brought up immunoglobulin in the context of splicing, I was worried that listeners might come away from the discussion thinking that splicing was the main way that B cells generate antibody diversity. While splicing does contribute to the ability of naive B cells to produce both antibody types IgM and IgD simultaneously, the main mechanism that B cells use to target pathogens with specific antibodies is VDJ recombination. VDJ recombination permanently alters the genome of each developing B cell in the region coding for the segment of the antibody that binds pathogens. This, in turn, results in a B cell with a unique specificity and the potential to be the founder cell for an eventual clonal population of cells with the ability to bind the pathogen. The process of developing an immune response in the lymph nodes helps to identify, select, and amplify the cells that produce antibody with the best ability to target each pathogen.

Thanks again for a such a great podcast!


Keith Garrison, Ph.D.

Associate Professor

Department of Biology

Saint Mary’s College of California

Shane writes:

Hi Vincent / Dick / Alan,

I found this site openpcr.org, which gives you the information you need to build your own PCR machine. They have a really nice interactive animation on how PCR works, you get to use a virtual pipette to put all the ingredients in the PCR tube and demonstrates what happens. It gives you a detailed breakdown on how PCR works.

Kind Regards,


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