Letters

TWiV regularly receives listener email with corrections, comments, suggestions for show topics, requests for clarification, and additional information. A selection of these is archived on this page.

TWiV 71

Jennie writes:

I wonder whether we have entered a new chapter in the book of human knowledge sharing. I’m often working physically when I listen to my favorite science podcasters (TWIV, TWIP and Mark Crislip)…. so your entertaining program is intertwined with raking leaves, loading wood, washing dishes (but NOT vacuuming). I hope that learning and moving can be merged in this decade through a more thoughtful use of tech.

I love the unveiling of your subjects over the course of time…the interaction of the two of you is very important in peeling the layers…both of you ask each other good questions and your model is VERY important – neither of you is afraid of appearing ignorant by either asking questions or not knowing an answer.

Other aspects that you are modeling: the power of synergistic professional/personal friendship and the sublimation of professional rivalry that can humanize science and extend knowledge boundaries.

For years as an RN I’ve taught health care to people with a high school education (maybe not HS sometimes)…the wedge (or funnel?) of narrative is by far the best way of getting the information into their skulls. Stories, pictures and practice actually.

Your stories are the best!

Take good care of yourselves: walk where you want to go this year, eat more vegetables, have fun in the physical world and….GO GET EM IN 2010!

Your listener
Jennie

TWiV 70

Tom writes:

I just finished listening to the Original Antigenic Sin episode where you were talking about Wolbachia’s protective effect against virus infection in Drosophila. I was delighted that you were speculating about the effect in bees because Wolbachia has been one of my favorite subjects for years.

Some key things to know is that:

1. Beekeepers have used (overused) tetracycline routinely since I think the 1950s against a bacterial disease of the brood called American Foulbrood. This usage has almost certainly cleared any Wolbachia infections in domestic bees, if they once had it. Interestingly, we now have developed bees that are resistant to that disease, which make antibiotics unnecessary, though unfortunately they are still widely applied.

2. Wolbachia has been found to be very common in African bees (but only in Africa) in at least two subspecies. One of these races, Apis mellifera capensis, has the unusual trait of worker bees producing diploid (female) offspring parthenogeneticaly, possibly due to an effect of Wolbachia. Our European workers can only produce haploid offspring, which are always male.

3. Another well studied Wolbachia effect is something called cytoplasmic incompatibility. This can result in sperm produced by infected males killing eggs of uninfected females. Infected females on the other hand produce viable offspring using either infected or uninfected sperm. This gives infected females a huge reproductive advantage. Wolbachia is very selfish, and since it is passed on only maternally, in the cytoplasm the egg, it uses the genetically dead end male to kill off the competition.

My own pet hypothesis is that this could explain how descendants from 26 African honeybee queens released in Brazil in 1956 were able to make a nearly complete genetic sweep all the way to the southern US. Supporting evidence for this hypothesis is still lacking, since Wolbachia has yet to be found in this hemisphere, we are actively looking though. If found, it could be very useful not only for the possible protection from virus, but also for driving good genes into the population.

A person who we are working with to find Wolbachia in bees is David Schneider at Stanford. Here’s a quote from his article in Science last year,

“One might guess that an insect would be safe from having its microbiota altered. Honeybees are an exception, however, because we’ve been dosing commercial colonies of bees with antibiotics for decades. Before the rise of colony collapse disorder, one of the most important honeybee diseases was American foulbrood, caused by the bacterium Bacillus larvae. To deal with this threat, many beekeepers prophylactically treat their hives with tetracycline derivatives—the same antibiotics used to cure flies of Wolbachia. If these treatments cured queen bees, then all hives descending from these queens would also be Wolbachia free, because the microbe is transmitted maternally. A Wolbachia-virus sensitivity experiment may have already been performed on honeybees nationwide and may change the way bees interact with previously characterized pathogens.”

I find you and Dick brilliant in the way you come up with great ideas on the fly. It’s a pleasure to listen to such intelligent people bounce ideas around. Thanks for such interesting program.

Sincerely,

Tom

TWiV 60

Eric asked for “advice on how to bridge the gap between clinical medicine, public health, and virology research.” I asked Scott Hammer MD for his thoughts on this question. Here is Dr. Hammer’s response:

Hi Vincent:

Thanks for forwarding this comment. In response, I’d inform your interested listener that the career opportunities in Infectious Diseases are broad and include – fundamental laboratory research, clinical/translational research, clinician/teacher role at an academic center, epidemiology and public health (both domestic and international), private practice, and industry. A substantial proportion of Infectious Disease Fellows are pursuing Masters degrees in Epidemiology at their colocated Schools of Public Health so that they have formal training in both ID and epi/biostats/study design/global health, etc. For more information, I’d refer him to the following websites: the Infectious Diseases Society of America (www.idsociety.org), the American Society for Microbiology (www.asm.org) and the Association of Schools of Public Health (www.asph.org). In addition, he could surf the websites of some of the individual fellowship programs (Columbia, Partners (MGH and Brigham in Boston), Johns Hopkins, the University of Washington in Seattle, and the University of California San Francisco.

Hope this is helpful.

Best regards,

Scott

TWiV 59

Nick writes:

I’m a bit behind in my Twiv listening, but I’d like to comment on something you said in Twiv 47. You have reminded us several times in the past that “viruses are not alive” and you embellished on this during Twiv 47 by saying that if they are not alive, they can’t be killed. Actually, viruses can be killed, by treatment with formaldehyde or chlorox, boiling, or irradiation with x-rays or UV light. These are commonly-applied treatments that “kill” viruses. Were they alive before having been killed? Perhaps that is just a semantic question, but it seems to me that you cannot kill something that is not alive!

I think there may be some confusion in our minds about what a virus is. We most often think of viruses as being the virus particle, or virion, which carries the viral genome, wrapped in a protein and sometimes a lipid coat, from one cell to the next. This looks inert and not living. But this is a bit like saying that an oak tree is an acorn, or a sunflower is a sunflower seed. Viruses actually exist not only in the form of virus particles, but also in their intracellular forms, during which they carry out the many intricate and complex activities that lead to their reproduction. Sure enough, they need lots of things that cells provide, including energy, the machinery that makes proteins, and basic building blocks such as amino acids and nucleotides. But if you mean that “being alive” implies coding for those proteins and RNAs needed to synthesize proteins, produce energy, and make amino acids and nucleotides, this becomes a bit of a techical argument.

What about other “obligate intracellular parasites” such as chlyamydia and rickettsia? They can only reproduce inside cells, in part because they cannot synthesize certain amino acids and nucleotides. These organisms do make their own ribosomes and protein-synthesizing machinery, and reproduce by cell growth and division once inside an appropriate host cell. But are chlamydia elementary bodies (the infectious form that transports the chlymadia genome from cell to cell) alive? Are acorns and grains of wheat alive? The answer is yes, because they can reproduce under the right conditions; within certain cells, for chlamydia, and under certain conditions of humidity and temperature, for acorns and grains of wheat.

I argue that viruses are just as alive, simply that they have less of the equipment of life and depend more strongly on the host cell to provide this equipment. The recent sequencing of the genome of a monster virus, mimivirus, as well as the genomes of a number of other big viruses, brings viruses even closer to cellular life. Some of these viruses have more DNA and more genes than the simplest forms of cellular life. Mimivirus has genes for amino acid and nucleotide metabolism and for some parts of the protein-synthesizing machinery (but not ribosomes or energy production).

At any rate, I’m not comfortable with the notion that viruses are not alive. They are certainly part of the “biosphere” of living things. They share with other organisms the basic mechanisms of replication and expression of their genomes. They can reproduce themselves (with a little help from host cells), control many cellular processes, and undergo mutation and Darwinian evolution. Viruses have sex: they can recombine or reassort their genes. They can even have sex with cells, in both directions: viruses can insert their genomes into the cell’s genome, and they can pick up genes from host cells and integrate those genes into the viral genome.

Viruses may have originated from cells, or alternatively could have played a role in the origin of life, before cells as we know them existed. RNA viruses and viroids may even be evolutionary relics of the RNA world, which is thought to have preceeded the present world in which all known cellular organisms have DNA genomes. DNA viruses could have played a role in the transformation of cells from RNA to DNA genomes, by having introduced DNA genomes into RNA-based cells. For a fascinating argument in favor of this theory, see “Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: A hypothesis for the origin of cellular domains” by Patrick Forterre [PNAS March 7, 2006 vol. 103 no. 10, 3669-3674].

If you can kill it, it must have been alive!

I just listened to Twiv 48: your further discussion of this topic was interesting but sort of stalled. I got the impression that Rich agrees with me!

TWiV 57

TWiV 56

Joe writes:

TWIVERS,

Guys, what a great podcast. I am a chemical engineer with a MS in Environmental Management. I have been doing EH&S work in industrial settings for about 20 years after some years in R&D and manufacturing positions. I have always had a strong curiosity for all branches of science (physics, astronomy, electronics and biochemistry), as well as math and history. Emergency response and risk communication functions have always been part of my job over the years. Virology was relatively new to me when I found your podcast. I had spent quite a bit of time learning the state of the science related to avian flu and SARS so that I could gauge the level of preparedness my company should have for responding to a pandemic. I eventually concluded that we needed a plan and should be ready but that the H5N1 virus had some ways to go before it became a general threat to humans. That research had left me with an interest to learn more of the broader field of virology. When H1N1 hit this year in Mexico, I found your topical podcasts very helpful.

I have been rapidly catching up on your episodes as I drive (about 1 episode per weekday) and will be sad when I am forced to slow down to real time speeds. I don’t suppose you all have considered doing “Today in Virology” so that I will have a new episode each day!!!

To the point:

I strongly agree with your assessments of the limited value of face masks with respect to providing protection from airborne flu infections. Actual user practices leave many infection pathways open. Beyond just not getting a good seal, how do you train users to remove the mask without contaminating their hands and face. If you reuse the mask which would be necessary in an emergency, how do you keep the inside clean. When do you wear it and when do you take it off? I train people to wear respiratory protection in accordance with the OSHA requirements for fit testing, medical surveillance, industrial hygiene testing, etc. It will not be easy to translate those practices to an untrained inexperienced population.

I agree with Dick that the whole “hot and humid stops the spread of flu” dogma seems inconsistent with the facts. How do we know that flu does not show up in human stool? Do we have actual data? In Asia, could the transmission mechanism be airborne particulate avian feces? Could the reason the pandemic strains violate the seasonal rules be a function of increased intestinal transmission or conversely that their envelopes are more robust in withstanding environmental stresses? The great thing about science is that the more we learn the more questions we generate.

With respect to the study on flu transmission and absolute humidity, If I heard you correctly when you quoted the summary hypothesis of the paper, the authors proposed that the aerosol droplets float longer when dry. This set off my engineering “I doubt it” alarm! So I spent some time reviewing the basics of psychrometry and humidification. I have a new theory on why low absolute humidity correlates with transmission. I think the critical parameter is actually droplet temperature. Droplet temperature will be controlled by the Wet Bulb Temperature for any set of conditions. Wet bulb temp is the temperature of a wetted surface that is experiencing steady state evaporation into the local air conditions. The lower the Relative humidity, the faster the evaporation and more heat lost resulting in a cooler surface. Think swamp cooler in Phoenix vs. New Orleans. Let me give some data to elucidate:

(All data interpolated from Figure 12-2 of Perry’s Chemical Engineering Handbook 5th edition)

Take a volume of air with an absolute humidity of 30 grains of H2O per pound of dry air. (7000 grains = 1 pound) Sorry for the units, but I think in Fahrenheit!

@ 35 F = 100% Relative Humidity (RH) and the Wet Bulb Temp. (WBT) = 35 F (i.e., No cooling by evaporation)

@50 F = 55% RH WBT = 43 F

@80 F = 20% RH WBT = 55 F

As long as the absolute Humidity is low, the particle temperature will stay low until it dries out. In higher humidity, there will be little evaporative cooling and so a higher droplet temperature will be reached more quickly. My amateur virologist guess would be that the lipid coating has an upper temperature limit beyond which it loses strength and/or integrity. At higher temperatures and higher humidity the particle temperature gets too high for the virus to survive shear stresses related to contact with surfaces. In engineering terms it doesn’t bounce well if it is too hot! This would also be consistent with avian transmission routes via cold water bodies. I would expect drying rates at higher temperatures with low RH to be much faster and once the particles dry, their temperature would equilibrate to the bulk air temperature. This would be consistent with the data showing reduced transmission at higher temperatures. Do we have any data that would indicate if dried viruses are still infectious? The physics of these small particles is not straightforward. Also, none of this addresses how the properties of spit differ from pure water. If there is someone out there with the experience and the computer power, this could be an interesting research topic. Please include me in the Et. Al. part when you publish.

A couple of recommendations:

A great website for non biochemists wishing to understand the basics of DNA and RNA is DNAi.org. Great history, clear explanations and the coolest videos of translation and replication I have ever seen! When you watch an animated ribosome at work it makes you proud to be a DNA based life form!

A book for Dick: “The Great Mortality” by John Kelly; “An intimate history of the Black Death, the most devastating plague of all time” I found this when researching H5N1 and was struck by how it captures the social and environmental influences on the development of the plague and then the impacts of the plague on societies and their reactions. It puts some of the current responses to swine flu in perspective.

Future Topics:

Why all the differences in nucleic acid structures within viruses? What are the pros and cons of ssDNA vs. dsDNA vs. ssRNA+ vs. ssRNA- vs. dsRNA?

How does an encapsulated virus survive in the digestive system? My vote is for Hydrogen Bonding (the universal answer for all chemistry exams!)

Dick’s list of top ten vectors throughout history.

How and why retro viruses change our DNA. What’s in it for them? (yes I know I think they are alive!)

How about a session on rhino viruses since we can all relate to their impacts. Why so many, are the different strains new each year or just new to me, etc.?

PS. Doesn’t the Zoster vaccine qualify as one you take after infection like rabies?

Love the show and the latent humor

Joe

TWiV 55

Kevin writes:

Dear TWIVvers,

I was listening to TWIV episode #50, concerning the recent article from Ila Singh’s group about the prostate cancer – XMRV connection, on the same day the NY Times reported a study from Judy Mikowitz et al., finding an association between XMRV and chronic fatigue/immune dysfunction syndrome, aka CFIDS. The CFIDS story has been getting even more attention, due in part to the eagerness of patients and advocacy groups to contradict the common stereotype of CFIDS as a psychosomatic illness – what some people used to call the “yuppie flu”. I have no doubt that CFIDS is a “real” physical illness, and that it involves some kind of chronic infectious process; but as a computational biologist and professional skeptic, I suspect that the relationship between XMRV and disease is *much* more complicated than the people reading these stories are likely to believe.

Although the Singh and Mikowitz groups found strong evidence that prostate tumor cells and peripheral blood cells from CFIDS patients were more likely to harbor XMRV than controls, it’s still premature to assert that XMRV causes cancer or CFIDS. It’s equally probable that patients with both diseases have an immune deficiency, due to genetic or environmental factors or an infection with some *other* agent, that allows the virus to proliferate. Even if XMRV can be said to “cause” one or both of these diseases, the question remains: what is it that allows the virus to establish a foothold in some people but not others? This is of course something we understand poorly, for almost all viral pathogens, including your beloved poliovirus.

So I was intrigued when your guest Jason mentioned a mutation in RNAse L that he said was present in a large fraction of the prostate tumors, that could make the cells more susceptible to viral infection. I went online that night to look up the Singh and Mikowitz papers, and find out if the RNAse L mutation was found in the CFIDS patient’s cells also. It wasn’t – but as it turned out, Ila Singh’s group didn’t find the RNAse L association either. This was a larger, better controlled study than the 2006 paper from Joe DeRisi’s lab that did find the association, but I still have to wonder how the two groups came up with such diametrically opposite results. Any comments on this?

Also, I suspect I wasn’t the only listener who was confused by Jason’s statement that the mutation was found in the tumors, and thought this meant either that the virus was causing the mutation, or that the mutation was specific to the tumor cells. Since most listeners aren’t going to run home and read the original papers, perhaps you could clarify: the mutation we’re talking about is a variant of the RNAse L gene that some prostate cancer patients are born with and is a possible susceptibility locus – not something that’s specific to malignant tumor cells.

To end on a more positive note – I’ve been listening to TWIV for a few months now and have recommended it to many of my friends and colleagues. It makes my 45-minute commute to Livermore seem to go by in no time at all. I have lots of ideas for podcast topics – for one, it would be great if you did an episode focusing on viral strategies for evading our immune response. I would also love to hear your ideas about iPhone apps for virology research; I feel it’s really important to have ways to visualize and manipulate biological data that are both intuitive and beautiful. Thanks for all your hard work on the podcast.

Ben writes:

Hi,

I am not a scientist, researcher, or health professional, just a closet science-nerd who loves your show. I just had a few questions about viruses that I can’t seem to find answers for that I was hoping you could answer.

Are there virus-receptors on cells themselves? If so, why would a cell evolve a receptor to something harmful? How did viruses evolve in general if they kill off their hosts, that certainly couldn’t be a beneficial trait right?

How are viruses so infectious and damaging when they are merely an envelope of genes? Since they aren’t alive like bacteria I can’t imagine why they would exist just to kill things. The same goes with prions. There can’t seriously be an “infectious protein” can there? Proteins are just amino acids folds.

Hope you can answer some of these either by email or on your show. Thanks a bunch!

TWiV 48

Rodney writes:

Hello, I have been an avid listener of TWiV over the last 9 months or so and have very much enjoyed the podcast. It is always great to hear a broad, informed discussion on virology, and your recent podcast on viral classification was of particular interest to me. As a Viral Genome Curator at the National Center for Biotechnology Information (NCBI), I am currently working with the International Committee on Taxonomy of Viruses (ICTV) and several virology research communities in an attempt to address longstanding and emerging issues of viral classification. Your podcast provided a concise primer to this topic, but I thought it worth mentioning a few additional issues.

First off, all viruses are classified by nulceic acid, dsDNA, ssDNA, dsRNA, ect…, both by NCBI and ICTV. Although these divisions are given no rank, they provide functionally relevant handles with which to globally group viruses. Second, the way in which viruses are classified is somewhat variable. You might be surprised to know that despite developments in genomics, many viruses are still classified by morphology, using electron microscopy. This is particularly true of bacteriophages, and NCBI and ICTV are working hard together to develop more portable, computer based methodologies. However, it is worth noting that even when computational tools such as Blast and PASC are used to classify viruses, the line of demarcation that separate different “organisms” vary widely amongst different viral families. This variability may actually be a good thing as it allows different research communities to tailor taxonomy, making it more relevant to a specific group of viruses.

Perhaps the more pressing issues in virus classification arise as the traditional, isolate, passage, and physically characterize approach to viral discovery is altered by modern molecular techniques. In the past, viruses have been characterized by a number of criteria including host and disease. Yet, the proliferation of environmental sampling, emerging direct sequencing methodologies, and a greater appreciation of the broad host range of some viruses, creates a number of classification problems. For example, how does one know if a novel candidate genome gathered from a sewer or a biopsy is actually a virus? And for that matter, how does one know that the sequence at hand is a full-length, fully functional viral genome? The relevance of these questions grows every day as databases are filled with an increasing number of novel “genomes” obtained through these methodologies.

Of course, these direct sequencing projects do have a number of advantages. There is no need to passage the prospective viruses over host cells, so there is no laboratory adaptation to a particular cell line. Such open ended approaches also recover multiple isolates from a single sample, allowing one to track naturally occurring genetic diversity, and it is likely that the proliferation of new techniques, combined with good old fashion bench work, will fundamentally change our view of viral evolution and adaptation.

Take care and keep up the good work,
Rodney

Elliot writes:

The  International Committee on the Taxonomy of Viruses (ICTV) web site at www.ICTVonline.org provides access to a database of the current taxonomic classification of viruses as well as the definitions and guidelines used by the ICTV to make the classification. The taxonomic ranks used to classify viruses are the Order, Family, Subfamily, Genus, and Species. (There are 5 orders currently recognized: the Caudovirales, Herpesvirales, Mononegavirales, Nidovirales,  and Picornavirales.) All viruses are classified into species (including plant viruses), and investigators who study every recognized virus family are represented on the study groups that participate in the classification process (including plant virologists).

A viral species as defined by the ICTV is:

“… a polythetic class of viruses that constitute a replicating lineage and occupy a particular ecological niche”. A “polythetic class” is one whose members have several properties in common, although they do not necessarily all share a single common defining property. In other words, the members of a virus species are defined collectively by a consensus group of properties. Virus species thus differ from the higher viral taxa, which are “universal” classes and as such are defined by properties that are necessary for membership.”

Note that Poliovirus is no longer a species! It has been renamed Human enterovirus C.

As for how “different” a virus isolate needs to be to create a new species, this varies according to the virus family and varies especially according to the genome composition (DNA viruses vary much less than RNA viruses). Each ICTV Study Group provides species demarcation criteria specific for each virus family that define the criteria for establishment of a new species for that family.

Thanks for providing the opportunity for clarification. Love the program!

TWiV 47

Jesper writes:

Dear fellows of Twiv,

It is my understanding that us humans live in peace and symbiosis with some bacteria. Is there any such arrangement with any virus?

Another way to phrase the question; if all viruses were to be removed from the world, would we be better off?

A follow-up question, even more abstracted from the lab bench; if all viruses were gone, is it reasonable to believe that new ones would come into existence? How fast? From where? In one of the twiv episodes someone said “Any suffciently complex system has parasites”, so I assume given time something is bound to fill the niche of viruses.

All the best,

Jesper