Jon writes:

Dear TWIV gang,

In “TWIV 84: Gators go viral” (May 2010) you discussed oncolytic myxoma virus with Grant McFadden, and Vince asked (1:02:48) when he thought that such viruses would be used in the clinic. Grant was optimistic that oncolytic viruses would find clinical use, but didn’t want to get pinned down on estimating timelines, saying:

“Well, you know the road is littered with people who make predictions about where medical research is going and how long it will take to get there. I would say I don’t know what the long term will be but I certainly expect to see in my lifetime specific uses of oncolytic viruses for certain cancers, and as clinicians learn how to use them and scientists get more strategic in showing how best to use them that their uses will grow at some point in the future”

and later (1:04:23)

“I think there is a real likelihood a number of these viruses are going to find their way for actual treatment of real cancers in humans and I like to think it is in my lifetime”

Since 2010 there has been lots of progress made in Oncolytic virotherapy. Notably

1: Amgen has interim statistically significant (p<.001) durable response data from its phase 3 oncolytic herpes virus trial

and a statistical trend towards improved overall survival in a preplanned interim analysis.

2. Oncolytics Biotech announced positive interim tumor response data from stage 1 of its phase 3 trial of oncolytic reovirus (Reolysin)

The crucial data on overall survival is due out any day now, perhaps before this letter is read on TWIV. Furthermore, Oncolytics biotech has released a lot of data from single-arm phase 2 trials, for example in squamous cell lung cancer

metastatic melanoma

pancreatic cancer

and non-small cell lung cancer

3. In a dose-escalation trial of only 30 patients, Jennerex’s oncolytic vaccinia virus demonstrated a statistically-significant overall survival advantage in the high-dose cohort of its advanced hepatocellular carcinoma patients:

although it stumbled in a more recent trial:

With overall phase 3 data soon to appear from Amgen and Oncolytics Biotech, it is an exciting time for oncolytic virotherapy. I was wondering if the time would be ripe to ask Grant if he’d be willing to give some predictions on when we’ll see oncolytic viruses used in the clinic.

Please ignore this letter if this phase 3 data is already out and definitive by the time you read it.



PS. I have a listener pick of the week, a youtube video produced by a graduate student in string theory whose advisor could well be weird Al:

Josh writes:

Dear TWiV Doctors,

This morning I was searching for info about flu shots, specifically if the new formulations were available, and I found this on my first page of google results (a screenshot, please let me know if you cannot see it):

Screenshot 2013-10-13 08.31.49

As you can see, there is lots of great info, but something that Google calls an “In-Depth Article” from “Lew Rockwell” that says you shouldn’t have the flu shot, just take a bunch of Vitamin D. It also lists the article in the same category as articles from Time and the New York Times. Whatever criticisms can be leveled at those two publishers, they would never publish anything so ridiculous and putting them side by side just elevates the nonsense.

Makes me so Chang-ry! (Community TV show reference)

Ayesha writes:

ouch! A strong argument for science funding:

Maybe a pic of the week?

Jenn writes:

Hi Again All,

Finally got somewhat caught up. Just wanted to send my apologies for not being more clear with my book comments (“Men Against Death” is by Paul De Kruif who also wrote another great one called “Microbe Hunters.”), and for not catching Dickson’s pick of “11 Blue Men” by Rouche. Keep up the great work!



Franklin writes:

Hello Vincent and crew,

In this weeks TWIV #251 you mentioned that you had learned a way to keep MHC I &II straight – everything equals 8. Back when I was an undergrad I used a different memorization trick that connects more concepts for me . If there are visual learners in your audience I think this system might be easier for them to remember. I won’t take credit for the idea but I also don’t remember anyone showing it to me.

Have a great day and keep up the good work,



SIU School of Medicine


For helper T cells think about the shape of an H:

If you overlay other shapes on top of it

A 4 fits in it – CD4

Also a II fits in it – MHCII

Additionally the shape of the MHCII structure matches it




For cytotoxic T cells they don’t match the H shapes:


CD8 (unless if you grew up with just digital clocks)


Structure of MHCI



Sorry for my art work. I’m a medical student not an art student.

Peter writes:

Dear TwiV team.

First I would like to say how much I am enjoying Professor Racaniello’s Virology course on Coursera. It is 30 years since I studied any biochemistry so I am having to do a lot of extra reading to get up to speed. Looking forward to Virology 2 though.

I read of an alternative approach to providing broad immunity against influenza and would be interested on your views on this.

It is not a universal vaccine but rather sequential vaccination against different influenza strains:

According to Dr Scot Hensley, “Since we now know that pre-exposure events can influence vaccine responsiveness in a predictable way, we can begin to design vaccine regiments that preferentially elicit antibody responses against conserved regions of influenza virus.

We may be able to strategically vaccinate our children with antigenically diverse influenza strains to elicit antibodies against conserved viral epitopes.”

Presumably, since we can already produce vaccines against different strains it should be possible to test this approach in clinical trials fairly quickly. If successful the strategy could be implemented before the more experimental universal vaccines will be ready for production.


Eric Delwart writes:

Dear Vincent

i realize there is much news to pick from but i think the recent progress in the HIV vaccine front where inoculation with a CMV vector expressing HIV proteins rises above the noise. The fact that it lead to virus ERADICATION after viremia was detected in the inoculated animals is remarkable and quite a step forward from previous vaccination strategies. It may be the the chronic nature of CMV is what resulted in such effective immune responses and that chronic (rather than transient) vectors maybe the way forward for such viruses as HIV (and HCV).


James writes:

Kia Ora folks,

In TWiV 246 you talk about the agreement that was come to with the Lacks family and publishing the genomes of the HeLa cells. Firstly and quickly Rich mentions the German group then how “we’re” in an age of HIPPAA. No, the US has HIPPAA, other countries have different systems that can vary a lot. Coupled with universal public funded healthcare and the thought processes around the handling of genome data can be very different to what you would think.

Now onto the more thorny issue of the family. Yes the HeLa cells contain the same basic genome that is present in parts of the children and grand children. However how similar are they? The cells used were diseased and have spent decades mutating and being mutated in different ways whilst the descendants have ever shrinking parts of this genome and have the much more stable parts.

All the way back around TWiV 105 you mention the Personal Genome Project that will put in the public domain the genomes of people. Not the genome of some cancerous cell but the genome of healthy tissue. How can this person consent in the place of their descendants to have parts of their genome publicly available with detailed history of the person it came from? When do we say that a descendant has no further say in the release of data? For example the great great great grandchildren of Henrietta Lacks will only have 1/32 of her genome.

I do think the HeLa agreement is a useful stepping stone but it is far from the endgame as more and more of these genomes are released or leak out. As Alan said, it’s a flimsy barrier when there are so many ways around it even without access to the cell line to sequence yourself. And I seriously doubt that the final setup will look anything like what was agreed on with the HeLa genome.

Please don’t avoid these thorny topics as the discussion is important. 🙂




Aotearoa (New Zealand)

Richard writes:

Hello Vincent et al,

I really enjoyed hearing about the inner workings of the Principles of Virology illuminati. I wondered if it might be possible to share your list of often misused words and phrases in virology and molecular biology, as this is a topic with which many researchers struggle. I think the importance of precise and succinct language becomes especially important for biologists interested in education, where so often, we use phrases to cliche without actually understanding the detailed (and sometimes incorrect) meaning of our jargon. There’s a substantial body of discussion of some of these misused phrases (‘homology’ and ‘epigenetic’ come to mind), and it seems like your list of more commonly-misused terms might be of use to many of us.

Keep up the great work,


Maren writes:

Dear Twivers,

my name is Maren and I’m a PhD student in the Institut of Virology at the Free University of Berlin.

During my studies of Biology I majored in virology and I am currently working on Influenza HA.

After a long battle with myself I decided to finally take action and participate in your podcast.

As a listener Pick of the Week I would like to introduce you to my childhood heroes Maestro, Pierrette and Psi. All being characters of the fantastic cartoon “Once upon a time…life”

It is a cartoon series from the 90’s, which was aired all over Europe, but I’m not aware of it being aired in the US.

It as a french series that tells about the body, the cells, the immune system, basically everything you need to know to start a fascination with biology.

It is a very cute story for kids with all the heroes you will fall in love with, who defend the body against nasty diseases played by the story villains.

As a kid I just loved the stories and the characters, but watching it now again with my godchild made me realize, how scientifically accurate the whole thing was.

Just have a look at the DNA and RNA, it’s simple but still exactly how it should be.

Here is the link to the webpage, where you can find background information and all the other formats of the series:

link in English

In addition you can find all episodes on Youtube

I hope you’ll enjoy it with or without your kids 🙂

Greets from lovely Berlin, Germany 11 am, 20°C, sunny with a few small clouds

P.S.: There is a new podcast publishing platform rising in Berlin, which tries to help podcasters making podcasting as easy as possible.

They are still in beta phase, but keep an eye on them, it’ll be worth it 😉

Buck writes:

Hey Twiv folks,

My name’s Buck Trible, I’m a first-year PhD student at Rockefeller University, where I’m doing lab rotations and currently working in the fascinating world of CRISPR. I just came across this remarkable paper and thought to send it along in case you’d like a nice evolution story. The CRISPR system, as you’ve discussed on the show, is a sequence-guided adaptive immunity that allows bacteria to protect themselves against phage. Here we have a phage picking up the CRISPR system and using it to attack portions of the bacterial genome that confer resistance to the phage. Just incredible. It’s not wholly unlike the story of phages of cyanobacteria picking up the genes required to keep photosynthesis active, so they can maximize replication as they kill their hosts, which I believe was discussed on TWIM a while ago. Anyway, cheers!

Paper is here:

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