TWiV 220 Letters
Dear Vincent and company,
I am a dedicated follower and fan of your TWIV podcasts and, until now, haven’t felt compelled to mail into the show. I just wanted to say that your most recent guest, Dr. Anthony Fauci, was fantastic. He was insightful and interesting and I thoroughly enjoyed hearing a bit more about the clinical side of Virology. I grew up in South Africa and have a special interest in HIV/AIDS and it’s partner infections (in particular HPV) and Dr. Fauci’s insights into the subject were riveting. I really hope you get him on again.
I also wanted to say that your Virology podcasts have influenced my decision to do an undergraduate degree in Virology and Immunology at the University of Bristol (England) this year. I will, in fact, know if I have been accepted into the course in the next couple of weeks! I look forward to learning more about the subject and will continue to be an avid fan of TWIV.
WOW! Thanks for picking my poliovirus simulation outputs as a pick of the week, I’m really chuffed
It’s taken a couple of years to build these models and they are finally at a stage where we can start doing some really interesting things with them.
Some nerdy facts about the simulations:
1. The virus itself (wild Poliovirus type 1) takes over 1 million atoms to build and it takes about another 2 to 3 million atoms to simulate the water and ions surrounding the virus.
2. We simulate the virus using 16 thousand CPU cores but have used up to 32 thousand cores (roughly 16 thousand desktop computers).
3. It takes 2 to 4 weeks to perform a 0.1 microsecond simulation (depending on how much of the supercomputer we use).
4. To render the 9000 frames of output for the movie it took about 1 minute per frame (150 hours on my desktop computer) and 2 TB of data.
5. If you mess up the magnesium concentration in the core of the virus, the virus explodes at three times the speed of sound. Followed by hysterical laughter at the sight of an exploding poliovirus.
Cheers from Melbourne where it’s 22degC (72degF) with a light cool breeze and not a cloud in the sky
Jason A. Roberts
Senior Medical Scientist
National Enterovirus Reference Laboratory
WHO Poliomyelitis Regional Reference Laboratory
North Melbourne, Australia
I am a plant pathology grad student/mycologist at Wazzu (Washington State University) in Pullman, WA. I am also an avid TWIV listener!
I wanted to write regarding Alexandra’s question in the last episode regarding mycoviruses. While many “mycoviruses” are in fact viroids, that is, unencapsidated, infectious RNA molecules, there are some true mycoviruses which are encapsidated. There has been some very cool work done on these, especially as they relate to plant pathology and plant-fungus mutualism/commensalism/parasitism. I’ve attached a couple interesting papers on these topics which I found sort of mind-blowing. I’ve often hoped you all would review a paper about mycoviruses or have a mycologist/plant pathologist on the show. Please do!
As for you Alexandra, bachelor’s degree time is like a freebie! Use it to get tedious classes out of the way so when you are in grad school you can spend more time researching! Obviously if you can you should do research too but there will be plenty of time for that once you are getting your MS or PhD.
Thanks for all the food for thought,
It is currently an unseasonably warm 3 degrees C here and raining.
A research article “Evidence for negative-strand RNA virus infection in fungi”: (http://www.sciencedirect.com/science/article/pii/S0042682212005004) for one of your listeners, Alexandra, who asked about fungal virus:
“This past fall I took a course on ecology and biodiversity, and one topic we covered was Kingdom Fungi. I am curious about viruses of fungi — I have heard a little about plant viruses (tobacco mosaic virus) but I have never heard of a fungal virus.”
TWiV 218: Monkeys turning valves and pushing buttons (February 3, 2013)
I’ve been listening to your podcast for nearly 3 years now. At first, I was reading virology papers alone. A few weeks later, I discovered “Twiv” at Google by chance. Back then, I remember you suggested to introduce one new virus in each future episode. Gradually, more and more guests show up instead. What a great feeling to have wonderful companies talking about viruses~! And it feels Reeeeeeally good when Twiv actually picks The Papers that I am fascinated with. Very happy to be of some help at last. But I don’t know how to reach the curious mind Alexandra. Maybe you can.
Hmm, I will let you know if I really can get into a PhD program in virus-host interaction ~^^~.
Hello Vincent et al.,
Just wanted to thank you for responding to my letter on the show a few episodes back. I was the student pursuing a Master’s in Entomology and was confused about my qualifications for a PhD in Virology next fall. After listening to your advice, I recently applied to U of Maryland, U Penn, and Boston U. Keep your fingers crossed for me!
I wanted to draw your attention to something that might be interesting for TWIM and TWIV. I especially think it’s something Rich might like, due to his fascination with Polydnaviruses. The link will direct you to a paper describing an obligate intracellular bacteria (Wolbachia) and its ability to induce resistance to Dengue virus in Aedes aegypti mosquitoes. Wolbachia is estimated to be present in >70% of insects, making it one of the most common parasitic microbes on the planet. In mosquitoes, Wolbachia induces an interesting reproductive phenotype termed “cytoplasmic incompatibility” where females infected with Wolbachia can produce viable offspring with both Wolbachia-infected and uninfected males. However, uninfected females can only produce viable offspring with uninfected males. A “lock and key” analogy is typically used to describe this phenomenon (male sperm is “locked” by Wolbachia and only females infected with the same Wolbachia type can “unlock” the sperm). Ultimately, this gives Wolbachia infected females a 2:1 reproductive advantage over uninfected females in a population. This has spurred interest in using Wolbachia to replace wild-type populations with a mosquito population that has a gene/genes of interest. The story is complicated, so I hope you understand the general idea! What I wanted to point out to you was that new research shows us that Wolbachia not only alters reproductive phenotypes, but other physiological aspects of the insect as well. One of the newer findings is that Wolbachia seems to bolster the insect’s immune responses to some viruses. I have attached a paper where researchers in Australia have released Wolbachia-infected mosquitoes to suppress Dengue transmission in the field. I thought the discussion of this topic might be timely, and could spark conversation about cross-disciplinary collaboration (for those listeners who enjoy virology in conjunction with another area of study).
I work with bed bugs now, but this topic/mosquitoes used to be my area of specialization. Hope you all find it as interesting as I do!
1. http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000833 (The Endosymbiotic Bacterium Wolbachia Induces Resistance to Dengue Virus in Aedes aegypti)
2. http://www.nature.com/nature/journal/v476/n7361/abs/nature10356.html (Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission).
It’s been a while since my last letter (by the name of Sasha on episode #178, http://www.twiv.tv/2012/04/08/twiv-178-t-sharp-on-how-tequila-mosquito/), but I have since become more more of a Virology geek turned programmer than the other way around.
The tragic suicide of Aaron Swartz on January 11, involving his alleged intent to release documents from JSTOR has sparked a response which I think the scientific community at large should know about: #pdftribute. Researchers in all fields of science have begun to release their papers on Twitter, open access, under that hashtag.
There’s speculation elsewhere in the tubes that this response to Swartz’s death might lead to the rise of alternative publishing models, such as those in PLoS ONE. What are your thoughts on this?
And I’d like to close with a quote attributed to the late activist, which I heartily agree with, and hope that you’ll enjoy the same.
“Be curious. Read widely. Try more things. I think a lot of what people call intelligence boils down to curiosity.”
[see Be curious]
Happy New Year TWIV’ers.
I have written to TWIV before to share my science related movies. Thus, I’d like to thank you for discussing my movies during the show. It’s a huge honor to have the TWIV team simply mentioning them, let alone discussing the them during the show. Thank you so much indeed!
I come here today to share my opinion on the Tamiflu issue involving the Cochrane Collaboration and Roche.
As mentioned before, I’m a virus researcher currently working on my second postdoc at the University of Otago in New Zealand. Prior to this position, I was employed as a researcher by a private company involved in the business of cancer detection using molecular biomarkers. Despite resenting having working for this particular company from a career’s perspective, I must admit that the experience I gathered was invaluable.
As you’d expect from a company involved in population diagnosis, we had to tip our toes into the world of clinical trials, which is an experience I doubt I’d have had in the academic sector. Comprehensive clinical trials are very complicated, multifaceted, horrendously expensive, and thus unaffordable/untenable to most academic labs.
Once immersed into the world clinical trials, I quickly realized that the system is flawed, to say the least. To be succinct, novel drugs that enter clinical trials are often (i) compared to placebo (in other words, drugs are compared to nothing, as opposed to the best medication currently available on the market); (ii) trialed in a small sample group (2000-3000 is usually the magic number); and (iii) trialed for a short period of time (6 months to 1 year).
Other problems include: the sample group may not include a comprehensive representation of the population ethnicity; the safety of the drug is often established based on basic physiologic symptoms such as blood pressure and/or cholesterol levels, leaving side effects to be detected well after the drug has been put on the market (from the top of my head I can cite the string of anti-obesity drugs such as Dexfenfluramine and fenfluramine, both removed from the US market in 1997 following reports of valvular heart disease and pulmonary hypertension, as well as Sibutramine, removed in 2010 because of increased risk of myocardial infarction and stroke); non-randomized and/or non-blinded trials (!); failure to report negative results or results that don’t conform with the expected clinical outcome…
The Cochrane Collaboration vs Roche saga regarding the full disclosure of all clinical trials involving Tamiflu is a well-documented case that has parallels with other drugs removed from the shelves soon after they have been approved for commercialization. It’s the case of another anti-obesity drug known as Rimonaband [Despite known a bit about anti-obesity drugs, I’m not obese. I’m even shorter than Alan (5’7’’) but I’m 78Kg and a black belt/instructor of Brazilian Jiu-Jitsu ]. The Cochrane Collaboration wanted to investigate the safety of Rimonaband, as there were ‘anecdotal’ reports in Europe that the drug caused adverse mental effects on patients. Thus, the Cochrane group requested that the pharma company hand in all results of the clinical trials involving the drug. As expected, the company said NO. Over 3 years, repeated requests from the Cochrane Collaboration were met with negative results, and each time the company would cite different reasons for not disclosing the results. Eventually, the drug was taken off the shelves by the pharma, as it was found to increase the risk of suicides. Did the pharma company know that during their clinical trials? To this date, we still don’t know!
The fact that negative results are not likely to be published is not new in science and, in my view, plain wrong. Nevertheless, not being able to test/investigate someone else’s finding goes contrary to the scientific methodology. How would you react if you have a colleague who publishes several papers on a supposed ‘novel’ virus which is not known to other research teams, nobody else has it, nobody can test the findings, tell you that you can’t have that virus and that you have to take his/her word for that?
Sure, if you really wanted to know the safety and efficiency of a given drug, you could do it yourself. You could set up a team and apply for funding to conduct clinical trials on that drug. However, unless you have a gigantic ‘money sequoia’ growing in your lab that will never happen – in case you do, could you please spare a couple of seeds? Thus, the most affordable way to investigate one’s claims in this context is to request that the results of the clinical trials be shared so they can be independently investigated.
Enter the Cochrane Collaboration. They are an independent nonprofit organization consisting of a group of over 28,000 volunteers in more than 100 countries, set to organize medical research information in a systematic way in the interests of evidence-based medicine (quick disclaimer: I’m not part of the Cochrane Collaboration, I don’t get funded by them, I don’t even know anybody who’s part of that initiative. I’m just aware of them).
Couple of quick points:
I’m afraid I’ll have to disagree with Alan’s comment regarding loss of qualitative power if you have to strip some info from the patients’ records. Blinding trials is relatively straightforward and, in fact, should be a standard operative procedure in any reputable clinical trial. The argument of sensitive info in patients’ records falling in the wrong hands is usually mentioned in these situations. However, there are several mechanisms one can use to ensure that identifiable info be treated sensibly. These include a wide variety of solutions, including encryption and/or legal processes.
Finally, I accept that it’s often private money that funds these expensive clinical trials and that the data generated belongs to the company. The problem arises when that clinical trial data is used to persuade governments around the world to stockpile a given drug. 15 years of experience in science have taught me skeptical. If you say something is that good, prove it. If you’ve got nothing to hide, then show it. Let science have its final say.
Thank you very much for your efforts in communicating science. Like everybody else here, I simply LOVE the show and can’t get enough of it. Sorry for disagreeing. Blame it on my short-man syndrome.
PS: Did Dick make it to NZ? How was it? Please let us know in advance when the TWIV’ers are coming to our ‘town’.
Sorry, forgot to mention the weather:
In Dunedin, 18 C, unusually bright blue sky!
As an educator, I would love to be able to hand out models of virus capsids or protein structures while teaching related topics. Until recently 3d printed models have been expensive and delicate. Thus, it would be difficult to have enough models for small groups of students to use. New, inexpensive 3d printers (www.makerbot.com and many others) that deposit melted ABS plastic have come on the market recently and are quite usable for making these models. Thingiverse is a site where public domain creations are made available for 3d printing (among other things). Below are links to virus structure and protein domain models I have printed and I use in my teaching of biochemistry.