I've been having an enjoyable time on my commute lately catching up with TWiV. Today I listened to #26 (Poxviruses), which included a discussion of Tysabri and PML. I work at Millipore which sells many products that go into a MAb production train, including virus removal filters that are included in the process. When this Tysabri story broke, there was a minor hubbub here until we (the R&D Virology group) were able to advise everyone that the PML was almost certainly an opportunistic infection rather than a product contamination.
I mention this because the story made me wonder if you might be interested in biopharmaceutical virus safety as a topic for TWiV? One of the things we do is study ways to ensure that any virus that might happen to contaminate a bioreactor would be removed by the drug purification process. There are some interesting scientific and regulatory issues around this, including building of a representative scaled-down system, selection of appropriate model viruses, best methods for virus quantification, and concerns around impurities in the virus stocks distorting study results. I happen to have a "Blog" entry recently put out by my company that discusses about this last issue. ( http://bit.ly/awWInI or http://www.millipore.com/downstream/cp1/2010tour_blog )
Of course, "interesting" is always a subjective term, but if you think this might make a good topic sometime I would be happy to participate.
Incidentally, I share your interest in picornaviruses, at least a subset, having done my thesis and post-graduate work on Coxsackievirus B and the Coxsackie and Adenovirus Receptor (CAR).
Thank-you for the fantastic services you are doing for scientific and general community with both your textbook and the web-based educational initiatives . I have found TWiV and your blog to be great ways to stay dialed into the wider world of virology.
After listening to you for several months, I have become interested in viruses to the point that I chose to write my final essay in a composition course on them. Attached is the essay: "The 'Death' of a Virus." It was written toward a less virology-aware audience, but I thought you might enjoy seeing one person's view on viral "life" and his thought process leading to that conclusion.
Many thanks for your wonderful podcasts,
I wanted to write and let you know how much I rely on TWIV now for a lot of my virology news! I am not fully caught up on the TWIV episodes, but just finished the one on Dengue. You mentioned that there wasn’t any good models for Dengue in immunocompetent mice, and I was wondering if you had a chance to read a paper in PNAS that describes a dengue model in Balb/C mice (using a mouse adapted virus). It doesn’t say it in the abstract, but if you read the paper, they describe the model in detail, and the disease in these mice does look a lot like dengue in people. Perhaps you saw this paper and think this model is flawed? Could you give me your thoughts on this article?
I just listed to podcast 84 on oncolytic viruses and thoroughly enjoyed it. I agree that the topic warrants additional attention on your show when time permits. I was very glad that Grant McFadden spoke about Reovirus and its oncolytic properties, I only wished he talked about it longer.
The Dearing 3 strain of reovirus is the virus used in Oncolyticbiotech's Reolysin and is quite far along and showing great promise in cancer clinical trials when used in conjunction with existing drug therapies. The company first tried injecting Reolysin into tumors directly and they found that they were getting app a 70% response rate at the primary injected tumor and some minor responses at metastatic tumors. They then tried Reolysin alone systemically to get at all the tumor masses and were disappointed with the results getting only app a 30 to 35% response rate - the problem being that the immune system cleared out the virus before it could get to the primary and metastatic tumors. This led the company to start testing Reolysin with existing cancer therapies like cisplatin, carboplatin, taxanes and other front line cancer drugs first in petri dishes and then in animals and finally in humans. To their amazement Reolysin and the cancer drugs worked synergistically together boosting the response rates to be higher than either Reolysin alone or the cancer drug alone and boosting clinical response rates back to the 70% or so level seen in the intratumeral trials. The primary reason is probably because the cancer drugs ablate the immune system giving the virus a better chance to get to the tumors and also by making the tiumors beds 'Leaky' and more open to viral infection. It has taken at least 10 years for Oncolyticbiotech to get to the point where they are now in one Phase III clinical trial for head and neck cancers and most likely over the next two years to be in up to three more Phase III trials (probably for Ras+ lung cancers and Ras+ colorectal cancers and maybe sarcomas which have very poor treatment options and very poor prognosis). In addition to the Phase Three trials ongoing or to start the company has completed or is currently running over 20 clinical trials with more to start soon
Some additional points - Reolysin contains Deering 3 reovirus is a naturally occurring non-manipulated wild type virus. Reolysin is easily and cheaply manufactured in up to 100 liter batches (100,000 injections) with potential to scale up to 500 liter batches.
The company holds dozens if not hundreds of patents worldwide on viral treatment of cancers with reovirus and other types of virus both attenuated and non-attenuated.
App. 400 patients worldwide have been treated to date with Reolysin and the number has been snowballing in the last two years.
Reolysin is being tested in cancer centers in the US, Canada, Great Britain and Europe.
Reolysin is showing great promise and hopefully will be an approved ubiquitious cancer therapy within the next three years.
Thanks again for that Podcast.
Found the link to this (http://www.miller-mccune.com/science/the-real-science-gap-16191/) in Slashdot. Lots of comments there, and here. There's a link in the comments here to a similar Harvard Magazine article, also with many comments. I'm saddened to see few suggestions about how to improve the situation. You've probably seen one or both articles, but I wanted to be sure you know about them in case they are useful. Dunno if any listeners to TWIV or TWIP would benefit by knowing where to read them. Perhaps it's time for America to reinvent itself, again, but I don't see how to do it, except through innovation.
I just met with a friend of mine who recently caught dengue-fever. It's a rather rare disease in Sweden (30-100/year - http://www.smi.se/in-english/statistics/dengue-fever/). My friend caught it in Malaysia, working as a cameraman at the recording of the most recent season of the European version of "Survivor" (known as "Robinson" over here) - http://www.dowell-netherlands.com/2010/05/dengue-stops-robinson-expedition-in.html. Some 68 people caught it in one fell swoop, and they had to evacuate the entire set.
However, I was glad to be one of the few in his circle of friends who'd ever heard of the disease and even have some cursory knowledge in the field - and no, I did not override his doctor's recommendation on any point!. I did send him to TWIV#3 (http://www.twiv.tv/2008/10/02/twiv-3-dengue/) so he too could get more info from the experts.
Thanks for your effort in producing twiw and sharing your knowledge with me!
All the best,Jesper