Caleb writes:
Greetings Drs. Racaniello and Elde:
I first and foremost would like to thank you for the endless entertainment and education over the last 4.5 years. I remember where I was when the first episode of TWiEVO went live (pulling into the parking lot heading into the lab) and how excited I was to listen! This podcast has been with me since my Ph.D. began (September 2015) and has inspired me to explore fascinating evolutionary questions.
The first chapter of my dissertation has just been published (See attached), and I wanted to share it with you to show you how impactful your podcast truly is!
I work in a veterinary entomology lab where the majority of the research conducted is field-based (working on dairy farms or poultry facilities) to understand some aspect of an insect or arthropod biology to develop improved methods to control them.
My dissertation project strays far from the standard scope of what my PI traditionally has done. I wanted to figure out what was causing a strange form of insecticide resistance known as behavioral resistance in the house fly.
Without writing out my entire dissertation, behavioral resistance is the heightened ability of an organism to detect and limit contact with a toxic substance, perhaps as the result of a repellent or irritant property of the toxic substance, its formulation, or presentation leading to an aversive response. While behavioral resistance has been documented for more than 50 years in the house fly, no one has taken it one step further to try to understand the underlying mechanisms conferring this resistance.
The first chapter of my dissertation describes an old school selective breeding technique (house flies are not a model organism for genetic manipulation) in which we breed flies to exhibit this behavioral resistance phenotype, then do a suite of behavioral observation assays to characterize this resistance further.
This experiment, which took over 3.5 years of selective breeding, set me up to have the ability to do some exciting genetic and genomics experiments.
I have now completed the first autosomal linkage analysis of behavioral resistance to insecticide in the house fly (allows us to identify which chromosome(s) resistance factors are on) and am now collaborating with Jason Stajich (I believe Nels may know him) on a poolseq project (essentially an evolve and resequence) in which we sequenced both susceptible and behaviorally resistant flies to now look for genomic changes that may be conferring the resistance.
My dissertation would, in all seriousness, not be the same without your podcast. I drew inspiration from each episode to continue to push forward to better understand the biology behind what makes us tick!
Thank you again for all you do!
Cheer!
—
Caleb Hubbard
Ph.D. Candidate: Medical and Veterinary Entomology
University of California, Riverside
https://drive.google.com/file/d/12aw0W375ds1eEaIefFIiW9NftkQd1Ewd/view?usp=sharing
Per writes:
Dear Twivers and/or TwiEvos,
I’m just a protein chemist who has started working on virus-host protein-protein interactions. In the beginning of January, I got a tip from a virologist at my department to listen to Twiv and I have since been a devoted follower of your podcast. You have really helped me to better understand the virology field and how virologists reason, and for this I am extremely grateful, many thanks! I have also ventured into protein evolution, without a formal education in evolution, so I don’t know if this is a stupid question, but I take the risk.
It is clear from your discussions that SARS-CoV-2 has not evolved to become more transmissible, because there is no need (i.e., it wouldn’t provide a selective advantage) . But with all lockdowns and physical distancing, the R value has dropped in many places around the world, thus making it more difficult for the virus to spread, and possibly imposing a selection pressure for increased transmissibility. When I had thought about this for a while, I realized that this must happen to most viruses when there is an increased immunity in the host population, after vaccination or after the virus has swept through and infected a large part of the population.
Is there evidence that any virus has evolved within a host to become more transmissible due to fewer available hosts, which to a non-expert like me appears to represent a very strong selection pressure? If not, this must be exceptionally difficult and could perhaps be used as another argument that viruses rarely or never evolve to become “worse”. Or would such evolution be rare because the window is too small between high enough access to new hosts on one hand, and too few hosts to proliferate at all on the other? “Am I thinking correctly about this?”, as Rich would say.
Best wishes,
Per
PS
I tried to be concise, despite writing from Sweden!
Per Jemth
Uppsala University
Department of Medical Biochemistry and Microbiology
Uppsala, Sweden
Suellen writes:
I am not a virologist or any kind of PhD scientist — JUST a retired Oracle database administrator — but I want to weigh in on the “SARS-CoV-2 was created in a lab/escaped from a lab” controversy.
My answer to people who make that suggestion is to look at the evidence that was uncovered when the virus first surfaced. In the first days of the virus, it was thought it originated at a wet market in Wuhan. Why? Because the first four people who showed up at the hospital had all been at that market recently. I figure, if the virus started at the Wuhan lab, then the first group of people who showed up sick would have had some connection to the lab — maybe not employees, but certainly family members, associates, neighbours. After all, the point of the investigation is to find what the infected people have in common. Do they live near each other? Work together? Have a common associate who is also infected? That’s how the “it came from the fish market” origin story started in the first place.
And as for it having been engineered in a lab . . . well, I just had a — ahem, discussion (read: heated argument) with a friend (read: maybe former friend?) about that, too. So let’s say I’m a mad scientist, I told my friend. And I either want to intentionally kill people with a virus, or I just want to find out if changing a gene here and there can make it more virulent and/or more transmissible. What virus would I start with? Probably SARS-1, which was pretty darn transmissible and virulent. I would probably NOT start with a novel coronavirus that I just discovered in a cave, wet market, or wherever, and that I don’t know the virulence of transmissibility of. Actually, from what I’ve learned on TWIV and TWI-EVO, I would probably not pick a coronavirus at all, since they have that proofreading thingy (scientifically speaking) that would make my work harder. I’d probably use the flu virus, since I could make mutations easily and it’s a pretty darn good spreader.
So I am able to make better arguments, thanks to the TWIX podcasts. I make fewer friends, but that’s another story.
And one quick, non-coronavirus, question: Is cowpox still a thing? Like, does it even still exist? You all were talking on TWIV recently about smallpox (in terms of vaccination), and it got me wondering. It seems that, in the olden days, milkmaids and others who worked with cows got cowpox on occasion, but I have not heard of a case of cowpox in my lifetime. So wondering if it disappeared? Maybe the smallpox vaccine took care of cowpox too? Just curious.
Keep up the great work, guys. Love the shows, all of them.
Suellen in Roswell, GA (pronounced like Sue Ellen)
where it’s cold and then hot then cold again. Yesterday’s high was 65. Today will be close to 80. And our state is “open” but really and truly most of us are still in our bunkers. We’ll let the crazy rednecks test out the transmissibility and virulence of the virus for us!
Xiaoyu writes:
Hi Vincent and Nels,
I am a big fan of Twievo. Probably Nels still remembers me, he was on my thesis committee 4 years ago.
I went to college in Wuhan and my wife is from Wuhan. So this pandemic feels very personal to me.
I am very tired of the baseless Wuhan Institution of Virology (WIV) origin theory (the US origin theory floating around in China is even more ridiculous), and most of scientists rejected that because there is no evidence. As someone knows the city pretty well, here is my argument that it was not from WIV.
Lab pathogen leaks occurred before in China. Back in 2004 there was a SARS lab leak in Beijing (the original SARS), and the whole lab was sent to quarantine hospital (https://www.cdc.gov/sars/media/2004-05-19.html). Even last year there was a Brucella outbreak in Lanzhou (https://www.nature.com/articles/d41586-019-03863-z). In both cases grad students/staffs were infected. Most of lab leaks are like that, start from people working in the lab to others.
This time, no one from WIV was infected till February 2020. I think this is a strong evidence suggesting SARS-CoV-2 was not originated from WIV.
If you don’t believe the words from WIV, the spread pattern of COVID-19 in Wuhan city did not support the WIV origin. Wuhan is a big city with 11 million population, separated by Yangtze river, the biggest river in China. WIV is in the south, while the wildlife market, most of early cases and the hospital first report the disease is in the north. Many hospitals in the north were overwhelmed by fever patients in Dec 2019, while the big hospital close to WIV, Zhongnan hospital, was still remodeling ICU preparing for the outbreak in Jan. 6 (according on published interviews in Chinese).
I also have doubt about early patients. Remember, no one knew this virus, there was no test at that time. I don’t think we can rule out that these early cases started with a bad flu, stayed in hospital for treatment and subsequently infected with SARS-CoV-2. Unless the sample was taken in early December (which is rare for flu patients), I am skeptical of them. I still think the wild life market is the center of this spillover.
Please let me know what you think!
Best,
Xiaoyu Zhuo
Postdoc in Ting Wang lab
Washington University School of Medicine
David writes:
Dear Chroniclers of Progress(ion),
Here in western Massachusetts we’ve had three days in a row with the temperatures above 29.5 and people are complaining bitterly. When I see that Phoenix hasn’t seen a low below 29.5 for two weeks, I figure I’ll just suck it up.
In TwiEvo 57 Jesse says that he is interested in getting more into the evolutionary side of things, and I was reminded of that combinatorial biologist you had ( I’m sorry, his name escapes me) who essentially said that people who are trying to draw a line from pangolins to bats, where there are hundreds of corona variants, and somehow, by an extraordinary coincidence commonly found in fairy-tales, that is the one that gets into a human, those people are missing the point. It all comes from bats! Bats have been shedding corona virus into the entire mammalian population through deep time. When we ethnocentrically decide that this new one that is infecting humans is interesting, we will invariably find a corona in some other animal that is the closest match yet! Until we find another animal with an even closer match. Because bats have been infecting animals since forever and there will always be an animal with the closest match yet.
What I find puzzling is why is Chinese bats? Do they have a greater over-lap/interaction with humans than bats in other regions? Are the bats endemic to China especially good at bat-to-another-mammal transmission? Would bats in Seattle be good enough? Would crawling through caves and scraping bat guano off his hands and knees be a fruitful direction for Jesse to take his research?
Allie’s comment about antibody studies also got me thinking. Here they have a pretty comprehensive list of which mutations afford “good-enough” binding. In the interest of precluding all the possible escape mutations, one will want to block all of them. Of course, money is always an issue, and some antibodies will be better at blocking several mutations than others. How would one approach a problem where one is looking for antibodies that are good at blocking multiple mutations?
Thanks for all that you do,
Dr. Dave Jackson
Jordan writes:
On episode TWiEVO you were discussing possible mechanisms for recombination in coronaviruses. There is evidence that the exoribonuclease, nsp14, mediates recombination. There is a bioRxv paper by Mark Denison that gives good evidence this is the case. (https://www.biorxiv.org/content/10.1101/2020.04.23.057786v1)
Jorden Kass
PhD medicinal chemistry