Hunter writes:

Dr. Mingarelli,

I am so pleased that a veterinarian has joined the TWiV team!  I have enjoyed your contributions to the podcast despite your having to juggle your PhD work at the same time.  I hope you can access this link from the most recent JAVMA journal.  It is extremely scary and disheartening, as now we are endangering the health and welfare of our pets in addition to potentially increasing the risk of rabies in people.

This is the part that scared me the most:

“Results show that nearly 40% of the responding dog owners believe canine vaccines are unsafe, while more than 20% consider them ineffective, and 30% think they are medically unnecessary.  Notably, about 37% of the

dog owners surveyed believe canine vaccination could cause autism in their pets, despite a lack of scientific evidence supporting this claim.”

As a retired food animal veterinarian this survey borders on surreal.  Oh how far we (scientists) have fallen in the eyes of the general public.

Keep up the great work but I will continue to enjoy my pork 🙂


Hunter Lang, DVM

Prairie du Sac, WI

Eric writes:

Dear Vincent 

In TWIV 1091 Rich mentioned my use of the term “dark matters” to describe the large fraction of sequences of unknown origins found in complex biological samples such as the gut microbiome or wastewater.  Dark matter is a term I shamelessly borrowed from the field of astronomy which describes the missing mass needed to explain the structure of the universe. 

Typical metagenomic analyses identify biological species through sequence similarities to already sequenced reference genomes. In the pre-print from the Stanford labs novel computational tools were developed to identify short circular RNA genomes capable of folding into rod-like structure and encoding previously unknown proteins. A small fraction of the dark matter was therefore illuminated without reference to prior genomes and revealed the rather common existence of a new type of viroid-like “obelisk” elements. Of course some bioinformatics-based predictions will have to be tested using wet lab experiments likely using synthetic genomes.

Many more surprises are doubtlessly in store for young computational biologists interested in novel ways of mining the already immense and exponentially growing public sequence databases.  

Or as Vincent concluded: Seek (or rather Seq) and you shall find. 


Bob writes:

Re: The Dengue snippet article.

I could not read the Nature Medicine article, as I do not have a subscription.  I did read the abstract.

I wonder if there was some selection bias in this study, specifically, folks who were not very sick did not go to a hospital. While I never saw Dengue in my middle-American practice, I think the symptomatic treatment of mild Dengue would be outpatient acetaminophen or an NSAID, rest, and fluids. Just wondering if they only picked the more ill patients inadvertently.

Bob McCown, M.D.

Apopka, FL

Kurt writes:


Listening now for almost 3 years.  I’ve donated but other than that small gratitude . . . there are not words in English to acknowledge what ALL of you are providing.

So . . . I’ll try a little Russian – BOLSHOI SPASSIBO !

Now . . . in Ep 1084 you mentioned that 20% of cancers are caused by a virus.

Is this 20% of cases or 20% of known cancers – that could make a colossal difference and impact further research (and its clear value).

Gratefully yours,


Orange, it’s the new black Tour
Доверяй, но проверяй

Daniel writes:

Dear TWiV,

In Episode #1091: Skeeter poo and obelisks too, Rich said that you “can’t do phylogenies just with structures”, and Alan mentioned that you could use morphogenic techniques to solve that problem. Alan is very much correct there. In fact, scientists have been using such techniques for a few years now. As such, I thought this would be the perfect moment to talk about the blossoming field of “Structural Phylogeny”.

I’m not a structural phylogeneticist, but I am doing a PhD in structural biology and attended a meeting on the topic a few months back, purely out of interest. Structural phylogeny has been taking off in recent years with the advent of more powerful computational tools and predictive tools like AlphaFold. A range of different algorithms are available for computing pairwise differences between structures, and these are used to assemble distant matrices for phylogeny construction. Experimental structures are, of course, favoured. However, deep learning-generated structures can also be used to supplement these databases.

The most powerful aspect of structure-based phylogenies is their ability to probe deeper in time than sequence-based phylogeny. Specifically, while sequence-based homology in distantly related proteins is lost over time, structural homology can be detected in proteins that separated billions of years ago. Genetic sequences mutate, and amino acids are changed, but the actual base structure of a protein is usually maintained. This is comparable to how all vertebrates have the same basic body plan, which has been modified over time to give a huge diversity of vertebrate organisms. Similarly, modifications to a protein fold can give rise to a large array of different proteins with diverse functions.

I’ve seen structure-based phylogenies applied to viruses, for example, using the delicious-sounding double jelly-roll fold of the major capsid protein to develop a model of viral evolution. See for more information.

As you can probably tell, it’s still in its early stages, and there are some limitations, but structure-based phylogenies can be a very powerful tool in answering some tricky evolutionary questions. I’m excited to see where this sort of thing goes.

All the best,


P.S. Thanks for all you do at TWiV. I study virus proteins myself, but my background is more in structural biology, so this podcast has been super helpful in expanding my knowledge of viruses while I study. I’ve also discovered a love for viruses, so I hope to keep studying viral proteins for a long time.

Anne writes:

An interview with Reed Jobs, son of Steve Jobs, who started a venture capital firm to support cancer research.  Reed was studying to be an oncologist during his father’s illness.  He talks about why he didn’t complete these studies, but also why he has returned to fund innovative research.  From the description:  

“ In high school, Reed Jobs was a summer intern in oncology labs while his dad, the late Apple co-founder and tech icon Steve Jobs, was battling pancreatic cancer. In his biography, Steve is quoted as calling his son’s interest in biotech the “silver lining” of his illness – and making cancer “non-lethal” has become Reed’s life mission. In 2023, he spun off the venture capital firm Yosemite from Emerson Collective (the philanthropy and family office founded by his mother, Laurene Powell Jobs) to focus on cancer research and biotech. Kara and Reed talk about the research-to-start up pipeline, how he’s been influenced by both of his parents, and whether AI, mRNA or CRISPR will be game changers for cancer patients.”