Blog to accompany Vlog 330, 3/14/2021

I made a video about the bio-engineered pig heart transplant. When my wife and I were talking about it a month ago, the patient was still alive and we were really rooting for him, and that inspired the comic (thanks to Cygnus Design for the artwork). It’s too bad the poor guy died in the mean time, but he made a real gift to science by participating in the experiment.

In case you didn’t know, people used to use pigs to hunt truffles in the wild (the fungi, not the chocolates). But the pigs badly want to eat the truffles, so you have to fight the pig every time you find some. People have moved on to using dogs.

If you want to do a successful transplant of an animal organ into a person, you need to remove all of the molecules that produce an immune response in people. That has to be done at the genetic level. And that project has been in the works for decades.

The pig heart recipient survived for two months and his health improved for a while (relative to pre-transplant). That’s a big improvement over Baby Fae’s baboon heart (she lived 21 days and declined over that time). Baboons who received such GMO pig hearts have lived for as long as 900 days. So, the GMO donor pig is an amazing breakthrough, and will only get better from here.

What, exactly, has been done to these GMO donor pigs? Are they ‘humanized’ in some sense? And what does that mean in this context? I have not been able to find peer-reviewed research on the specific genetically engineered pig that served as a heart donor – that work was performed at the University of Maryland School of Medicine.

The best information I got came from “First Clinical-Grade Porcine Kidney Xenotransplant Using a Human Decedent Model” in the American Journal of Transplantation.  It covers very similar work at the University of Alabama. The gene that codes for the attachment of the famous alpha-gal antigen have been knocked out. That’s the most famous pig antigen that basically everyone has a strong immune reaction to. But 9 other critical changes are covered by the paper.

They inserted 6 human genes [DAF CD46 TBM, EPCR, CD47, HO1]. These were chosen to help the heart’s cells appear more human to the immune system. CD47, for instance, is involved in cells sensing their environment. For reasons I don’t understand, CD47 is up-regulated in cancer cells and helps them avoid being destroyed by the immune system. That’s pretty wild – proteins that help cancer cells survive (that’s bad!) have been co-opted by humans to help pig hearts survive (that’s good!).

They also knocked out four pig genes [GGTA1 β4GalNT2 CMAH and GHR]. GGTA1 is the one responsible for transferring apha gal. GHR is the growth hormone receptor and knocking it out keeps the pig smaller.

Each one of these 6 human genes and 4 pig genes has a story – why was it added, why was it removed, how did it contribute. So this project is complicated with a huge amount of work going into it.

I’m excited for the future where anyone who needs a new organ can get one. And I’m even more excited for the version of that future where the organs are grown outside of sentient creatures.

Articles:

‘If you want the girl next door, go next door’: Lori Petty on Station Eleven and surviving – The Guardian
I have not seen much of Lori Petty’s new work, but I’m interested in Station Eleven, now. This article about a cool, unconventional path through Hollywood seems like a great adventure to have lived.

The Things You Bought But Don’t Own – Timothy Wood
This article is about how taxes pay for some content – like the DoD’s image archive – and so they release it into the public domain. But many state governments retain the copyright for the work they pay people to do. So when the cops document the exploits of Florida Man, we get to hear about it. But we are deprived the documentation of the similar adventures of Georgia man. And that’s too bad.

Putin Is a Fossil-Fuel Gangster. Clean Energy Could Cut Him Off at the Knees – Rolling Stone
When an autocrat can fund his operation from a state controlled resource (and the labor of a small minority of his people) he operates under a very different set of constraints than a president of a functional democracy. He needs to maintain tight control over that resource, his police, and his army. He needs to offer rewards to his keys to power. See The Dictator’s Handbook. The invasion of Ukraine is a natural extension. First, maintain control over the gas (both Russian gas flowing across Ukraine and frackable gas from under Ukraine). Second, hand out the spoils of war to your cronies. Third, purge the disloyal citizens and oligarchs. If we want to undermine this resource curse, we need abundant, decentralized energy (renewables and, maybe someday, fusion). We need energy that can’t be controlled by dictators. Also, carbon-free energy slows climate change. That’s the focus of the Rolling Stone article.

Academic Papers:

Porrett, Paige M., Babak J. Orandi, Vineeta Kumar, Julie Houp, Douglas Anderson, A. Cozette Killian, Vera Hauptfeld-Dolejsek, et al. “First Clinical-Grade Porcine Kidney Xenotransplant Using a Human Decedent Model.” American Journal of Transplantation. Accessed February 26, 2022. https://doi.org/10.1111/ajt.16930.

Talou, T. et al. “Dimethyl Sulphide: The Secret for Black Truffle Hunting by Animals?” Mycological Research 94.2 (1990): 277–278. ScienceDirect. Web. 7 Mar. 2022. https://www.sciencedirect.com/science/article/pii/S0953756209806308

Sade, Robert M., and Rupak Mukherjee. “Ethical Issues in Xenotransplantation: The First Pig-to-Human Heart Transplant.” The Annals of Thoracic Surgery 113, no. 3 (March 1, 2022): 712–14. https://doi.org/10.1016/j.athoracsur.2022.01.006.

Pence, Gregory E. (2008). Classic Cases in Medical Ethics (PDF) (5th ed.). Archived from the original (PDF) on April 18, 2016. https://web.archive.org/web/20160418213419/http://www-bcf.usc.edu/~bwrobert/teaching/mm/articles/Pence2004_Ch14.pdf

Videos:

Understanding Ukraine, Russia, and the War in Historical Context
This was a great summary. John Green does it again.

360° aerial bullet-time light-painting
I love a good photography trick – light painting is great. This takes it to the next level.

Tool Use Sparks Friendship with a Young Crow
Here’s a remarkable video. Young crows are not usually trusting. I’d love to know what this bird’s history was. Last fall, I saw a young crow fly into a window. I went over to see if he was OK, and his crow-friends got VERY mad at me for getting too close. He got up and flew off eventually. But his friends yelled at me for the rest of the season every time they saw me.

This lamp can hurt you in two ways
Cheap AC circuits can store a nice big charge, so be careful. Also, deep UV causes oxygen in the air to become ozone which is also a bit toxic. Also, deep UV will damage skin and eyes pretty quickly. Basically, don’t buy germicidal lamps unless you know how to use one (and maybe don’t buy grey market bulbs at all).