Brian writes:

In TWIV 1179, Rich described how an AI program uses structure to detect unknown virus. Different DNA or amino acid sequences generate the same protein structures. Alan mentioned this is convergent evolution. But not always. Prokaryotes integrate sequences laterally. Evidence suggests they use structure to preferentially integrate certain ones, probably as way to repair damaged sequences. If the structure fits, use it. Structures with different sequences, in prokaryotes, may do similar things. This may not be convergent evolution; a clever bacteria is doing something more like eukaryotic sexual selection.

Thanks for all your great work!

Brian

Len writes:

Dear TWIVers,

I was amused to hear you relate the Zinder story on a recent episode. I teach research ethics at UCONN, and in the module on data sharing responsibilities, Peter Setlow and I have used that story as a case study discussing the ethics of withholding research resources from the scientific community, as well as the ethics of obtaining such resources without appropriate permission. It’s a perfect story to address both ends of that ethical spectrum.

As a virologist whose career path took him into academic administration, I have thoroughly appreciated listening to TWIV and stirring my old virologist bones that had lain dormant for so long. You’re doing important work, and doing it well.

Best wishes,

Len Paplauskas

AVP Research (Emeritus)

Instructor, Dept. Public Health Sciences

UCONN School of Medicine

Sharon writes:

Hello TWiV team,

I was intrigued to hear alpha-1 antitrypsin deficiency (A1ATD) mentioned on TWiV. I’m a virologist, and I have some experience with A1ATD from my work in an assay development lab at National Jewish Health (NJH) in Denver, CO. NJH specifically sees patients with pulmonary, immunological and cardiac diseases. Our lab focuses heavily on infectious diseases (especially mycobacteria and other lung pathogens), as well as other lung diseases, like A1ATD. Your listener Rachel wrote in about episode 1167 in which Dickson mentioned what both Rachel and I presume is A1ATD. 

I wanted to follow up on Rachel’s great A1AT summary with more additional information related to A1ATD. A1ATD is quite common; 1 in 2500-5000 people of European descent have A1ATD. It’s encoded by SERPINA1, which is a highly polymorphic gene. The degree of disease progression depends greatly on the SERPINA1 mutation (there are many pathogenic mutations!—40+) and environmental factors. Not all mutations cause the protein to get trapped in the liver, but some mutations result in the protein not being made (null) or proteins released in the circulation with reduced inhibitory function. Mutations that confer A1ATD are the only known genetic causes of chronic obstructive pulmonary disease. A1AT’s main target is neutrophil elastase (NE); it inhibits NE activity mainly in the lung so that NE is not over-active and lung architecture is maintained. It is an acute phase protein that helps reduce NE activity post-infection. People with A1ATD are much more susceptible to pulmonary infections or pulmonary exacerbations from air pollutants, for example. I wasn’t sure about Rachel’s question regarding her pulmonary nephritis, but I found this paper (The pathologic spectrum of the nephropathy associated with α1-antitrypsin deficiency – ScienceDirect) that suggests a link, and especially in ZZ patients (severe A1ATD), which is probably why her physician mentioned a kidney biopsy. I also found this from another article: “Associated glomerulonephritis is unusual although it is well-recognized in children and young adults with the severe phenotype.” from “a1-antitrypsin (A1AT) deficiency presenting with IgA nephropathy and nephrotic syndrome: is renal involvement caused by A1AT deposition?” S.M.S. Ting1, T. Toth2, F. Caskey3, Clinical Nephrology, 2008. 70 (159-162). Please pass this information along to Rachel. We have lots of great docs here at NJH that specialize on A1ATD if you ever consider doing an Immune episode on it.

Wishing you all the best in 2025! Thank you for keeping me up to date on the most recent virology advances.

All the Best,

Sharon Kuss-Duerkop, Ph.D.

Senior Scientist | Strategic Innovation

Advanced Diagnostic Laboratories

National Jewish Health

Mollie writes:

Dear TWiV team,

I just wanted to write and say thank you for the work you do to help make science, and specifically virology, accessible to a general public audience – including colleagues working in different fields! I just finished a PhD on the politics of emerging infectious disease surveillance and response. While we have different politics, and I sometimes wish TWiV would cite experts from history, geography, or political science departments when discussing those topics (just as you insist people listen to scientists when speaking about science), the podcast was enormously helpful for making sure I was accurately describing infectious disease science while writing my dissertation in human geography. 

Your clearly explained debunkings of the various lab leak hypotheses of SARS-CoV-2 origins have been especially invaluable. I’ve recommended them to colleagues numerous times. On the left, I see a lot of people entertain versions of the lab leak theory because they have been harmed by medical practitioners or government institutions charged with protecting them – or because they study the very long histories of violence carried out by these institutions against non-white people, disabled people, queer people, and others. (For example, the 1927 Buck v. Bell decision legalizing the forced sterilization of disabled people in the United States has never been overturned.) I mention this because I think for this segment of the population, it’s not a matter of “not understanding science” because the problem is that many folks have a well-founded and deep-seated mistrust of many government, medical, and public health authorities. So as much as I want to pull my hair out when I see (for example) respected, award-winning investigative journalists entertaining versions of the “lab leak theory”, I also sort of get it. The way I’ve personally had luck reaching people who are coming from this perspective is to acknowledge, first and foremost, that their distrust makes sense. I then help walk them through some of the structural drivers of health inequalities and failed public health responses relevant to COVID-19 so they can understand how things like the lab leak theory actually distract us from addressing those problems. And then I also (of course!) direct them to relevant TWiV episodes so they can better understand the science. (For other academics, it’s especially effective to tell them that one of the Science papers establishing evidence for a market origin passed no fewer than five peer reviewers. I don’t know if people who haven’t been through peer review appreciate just how difficult it is to satisfy two or three peer reviewers, let alone five!)

Anyway – in sum thanks again for all that you do!

Best,

Mollie Holmberg

Postdoctoral Fellow

Balsillie School of International Affairs

Wilfred Laurier University

Wilfrid Laurier University occupies the Ancestral and treaty lands of the Neutral/Attawandaron, Anishinaabeg and Haudenosaunee peoples.

Sarah writes:

The Extremophile Campaign: In Your Home  (ECIYH) citizen science 

https://citsci.org/projects/the-extremophile-campaign-in-your-home

Might have found Thermus aquaticus in home hot water heaters. “If anyone had thought to look.”

After signing up on the CitSci website, and then for the extremophiles project in particular, participants are prompted to take photos of “slime, crusty mats, stringy growth,” in their homes, particularly in places that have extreme hot-cold cycles. Some recommended hunting grounds include washing machines, refrigerator drip lines, hot-water heaters, solar panels, and showerheads. 

If the researchers see something promisingly unusual, they’ll mail the volunteer a testing kit with empty sample tubes, gloves, and a scraper, and a prepaid envelope to send it back. Then, the researchers sequence the DNA of the sample, and the results will be added to an open-source database of microbes. By cataloguing the diversity of these tiny life forms, the hope is that some may one day become useful for human endeavors — like tackling greenhouse gas emissions, or cleaning up pollution.