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Cutting-edge xenotransplantation science manipulates cells at a precise molecular level. Its success rests on the sometimes messier relations between veterinarians and some very large pigs.

Ambient mood lighting? Check. Leather and latex? Check. Pheromones in the air? Check. A 300-pound boar and a team of veterinarians? Check. The scene is set for extracting some genetically edited semen.

I sit on a metal fence behind the gate of a large pig pen as Amelia jumps in to wipe down a leather contraption in the middle of the floor. A trained veterinarian now working in a biotechnology research facility, Amelia explains that this is a dummy sow used to help extract semen from the research facility’s boars. The dummy clean, she calls “We’re ready for him” to her colleague Jonas, another veterinarian on the team.

Jonas leaves the dimly lit room, and returns a few minutes later, herding a massive boar along the metal corridor and into the pen. Amelia sprays pheromones onto the dummy sow and leaps out of the pen to sit on the surrounding fence while the boar begins to shuffle around, sniffing the air and grunting occasionally. “He used to be a good breeding boar, but last time we looked at his sperm we hadn’t seen anything like it before!” she tells me. “It was completely clumped together and not moving. But we’re giving him another chance.”

As the boar begins to froth at the mouth and rub his snout on the dummy sow, Amelia and Jonas explain this is a great sign that “he knows what to do in the room.” They tell me that once he mounts the dummy sow, his physiology will be triggered and start to work “automatically.” It’s at this point that a vet will need to physically stimulate him so they can collect the semen they need.

The overarching hope is that their research will lead to the production of organs and tissues that will be routinely used for pig-to-human transplants.

Amelia perches on the fence of the pen, holding a plastic container with a bag inside it, ready to collect when the moment comes. We sit tight, and five, ten minutes pass… This is how vets spend many hours, waiting for boars to mount. Jonas cheers the boar on, offering support in German, “Geht schon, komm! Los geht’s Alter” (Let’s go, come on! Let’s go dude!). But Amelia grows impatient and announces she’s going to look for a female “for animation.” She returns disappointed: there were no “good” sows who could be brought in to arouse the boar. Time passes by without a successful mount.

Finally, the moment comes: frothy mouthed and breathing loudly, the boar mounts the dummy sow. A pink curly penis emerges as he thrusts towards the dummy. Amelia nimbly enters the pen, where she kneels to the side and stimulates him.

Unfortunately, the boar dismounts too quickly, without a finale, and Amelia quickly jumps back out of the pen. She describes how veterinarians need to be specially trained for this work with pigs, that it’s different from working with small animals or pets. “You need a strong hand for this,” she says.

The four of us continue this dance, me watching and quietly asking questions about the process, Jonas cheering from the sidelines, the boar mounting and dismounting, and Amelia stimulating him each time he mounts. Eventually, after over 40 minutes, they decide his time is up. With no ejaculation, this breeding boar has likely reached the end of his working life at the biotechnology facility. Jonas takes him back to his pen with a pat on the back and a commiserative ”Good try.”

Semen for science

The collection of genetically edited semen is one aspect of producing genetically edited pigs for xenotransplantation research. In recent years, xenoplantation science―the grafting or transplanting of tissues or organs from one species to another―has experienced what many researchers in the field are calling a revival, catalyzed by the so-called “CRISPR revolution.”

CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR associated protein) is a gene editing technology that reportedly enables the precise manipulation of genes within cells. It stems from discoveries on microbial immune systems where, for example, this technology is used to protect bacteria from viruses by creating a “genetic memory” to recognize specific stretches of genetic code that cells can rely on to detect and deal with viral threats. Practically, the system relies on two components: the Cas protein, which can cut DNA, and a guide RNA, which can recognize the sequence that should be edited. Using this, scientists can modify cells by first determining which part of the DNA needs to be changed, and then using CRISPR-Cas to cut it and modify the genes accordingly―for example, by removing or inactivating sequences (a knock-out) or adding in sequences (a knock-in).

At this facility in Germany, xenotransplantation researchers are experimenting with what kinds of multiple gene knock-outs are most effective at creating porcine tissues and organs that won’t set off a hyperacute immune rejection response when transplanted into another species. An α-1,3-galactosyltransferase (typically shortened to αGal) knock-out, for instance, refers to a carbohydrate found in some mammalian cell membranes, such as pigs, but not in human cells. Instead, human antibodies will respond when in contact with tissues that contain αGal resulting in an immune response. So, for successful xenotransplantation, it’s critical to inactivate the genes that code for αGal in pigs.

CRISPR has impacted the speed of research in xenotransplantation. Marc, a molecular biologist working on xenotransplantation, explained that with CRISPR, “I always do knock-outs with students within six weeks. […] When I was a PhD student it would take three years just to try to knock-out a gene, and now we can do it really fast and very easily.”

The edits made by these researchers support their experiments to examine xenotransplantation for various tissues and organs including heart and lung systems, islet cells, and more. To examine how the genetic edits impact organ function in the closest species to humans, researchers in Germany have transplanted pig hearts into primates. The overarching hope is that their research will lead to the production of organs and tissues that will be routinely used for pig-to-human transplants, reducing the number of people who die while waiting for a donor organ. In some countries, this research has already shifted from the lab to the clinic: in 2022, a man in the United States received the first genetically edited pig heart.

Credit: Charlotte Corden
Illustration of a big under operating theatre lights

In Germany, researchers are working to produce proof-of-principle evidence that their porcine organs would work within human bodies prior to moving into clinical trials, which they hope to enter within a few years. As this is still in the experimental phase of research, I shadowed interdisciplinary researchers working on xenotransplantation to better understand how this science is being performed, enacted, and understood by those in the field. I came to witness how the reproduction of genetically edited pigs is a baseline for this research process: without pigs there can be no experiments.

Getting physical

Genetic editing is only one piece of the puzzle in the quest to create or reproduce genetically edited pigs, as IVF or cloning methods are needed to transform those genetics into living beings. With IVF, semen is extracted (sometimes more successfully than our earlier episode in the pen) and used to fertilize eggs to create porcine embryos that are transplanted into surrogate sows who will then carry to term and farrow piglets.

While spending time in the facility, I had many conversations with researchers who would explain various steps in this process of reproducing genetically edited pigs. “We have to do a lot of mating, so collecting semen from the boars to then impregnate the sows, and so on and so on―that kind of stuff in the stables you know,” Paul explained. While Elsa told me that “We breed or clone them [the pigs] to try and get the right genetics for our work.” Always, the researchers’ emphasis was pragmatic, matter of fact; pig production was the routine course to acquiring the important stuff—the genetic material they need.

Although many biotech practices have become molecularized, and despite researchers’ straightforward narratives, the route to acquiring lively sperm tends to be a much messier, embodied, and tactile interspecies moment. To get to the genes, someone needs to roll up their sleeves, put on their gloves, and jump into the breeding pen.

Lively sperm, living boars

When semen appears “clumped together,” as Amelia described, it’s a sign that sperm mobility is impacted, which tends to lead to lower rates of fertilization. This is something that happens across species, but has drastic outcomes for these pigs.

As time in the pig pen ticked by, the vets’ voices became tinged with a note of desperation and dark humor, with Jonas’s cheers punctuating their discomfort. They knew that another unsuccessful round of ejaculate could put the boar out of the biotech business. Jonas, Amelia, and I were aware of the stakes of this interspecies encounter. While the jokes and encouragements were efforts to support the boar and themselves, the undertone was one of genuine concern. They were working not only to produce semen for research but also to prolong his life.

The veterinarians would reiterate to me how they never imagined ending up in animal research, that they entered veterinary medicine because they love animals and want to care for them. Faced with a situation layered with emotional complexities, these vets had to balance their professional veterinary and scientific duties along with their relationships to these animals. They had to perform experiments while simultaneously caring for animals they’d known for a long time and whose lives were in their hands―not unlike livestock vets working in the field who have to deal with animals as forms of capital as well as living creatures.

Amelia sprays pheromones onto the dummy sow and leaps out of the pen to sit on the surrounding fence while the boar begins to shuffle around, sniffing the air and grunting occasionally.

The extraction for which they are responsible reflects a somber reality of this interspecies relationship and the search for “good swimmers.” The employment of humor—the frisky encouragement in the pen, the playful reference to strong hands—can mitigate the more morbid aspects of a vet’s life in biotech.

Unfortunately for this boar, his history of static sperm and failure to climax rendered him no longer useful to the facility. Unlike in livestock agriculture, he won’t end up in a slaughterhouse or the food chain but in an incinerator for genetically edited animals.

Cloning as control

A few weeks after this failed attempt to collect semen, Amelia and I sit together at the lab bench as she performs somatic cell nuclear transfers (SCNT, otherwise known as cloning) with eggs and genetically edited cells. She tells me, as she stares through the microscope at a petri dish with enucleated oocytes inside it (eggs that have had their nucleus removed), that she prefers cloning over IVF. She says that although it’s not the most “natural” way to reproduce, she finds it comforting that there can be multiple scientific checkpoints throughout the cloning process. The kind of genetics the piglets will emerge with is clearer with cloning; the cell culture team can check all the cell lines, all the edits, before they’ve even created whole living animals. IVF is messier, there are more “moving pieces” to the puzzle, she explains. Researchers seemed to perceive cloning as a more controlled method, as a process they could more easily shape and command.

For cloning, you need a hand that is capable of delicately maneuvering pipettes, scalpels, and microinjectors. One that can skillfully slice cells, remove nuclei, and use kidney or lung cells to (pro)create. During fieldwork, I took an internship and learned how to clone cells, how to look through the microscope to delicately navigate microinjectors, introduce various compounds like calcium to help the cloned cells develop into embryos, and more. It takes a lot of time and concentration to work on this scale. But it is peaceful, especially compared to the lively experience of the stables.

With cloning, the physical experience for the veterinarians is one of sitting in a cool, quiet, brightly lit laboratory, void of frothing boars and dummy sows and the sensory stimulations that come with such multispecies encounters. Cloning removes some of the uncertainty experienced when working with animals and transfers it instead to cells and genes, a domain where scientific protocols can be implemented to try and influence outcomes. While sitting at a lab bench may not be the favored activity of these vets who deeply value their practical time with the animals, it does remove the burden of performance in the pen.

Not so boar-ing after all

Through all of this, I came to see that the collection of pig semen both disrupted and reinforced scientists’ narratives around the (re)production of pigs for xenotransplantation research.

Novel genetic technologies are implemented and understood by xenotransplantation researchers as a way of controlling or modifying life on a molecular level. But living beings don’t necessarily cooperate as expected or hoped. Sperm isn’t always lively, and boars don’t always mount. The messy uncertainties of research relationships and processes can be met with humor as veterinarians navigate complicated intimacies at the center of this research; or with alternative methods to minimize uncertainty, and even intimacy itself.

The collection of pig semen for xenotransplantation science continues while in the background there will always be the possibility of cloning as one biotechnological solution to the reproductive failures of boars, or, from another perspective, a potentially lackluster interspecies sex act.

Illustrator bio: Charlotte Corden is an illustrator and fine artist whose work often centers around what it is to be human. She has an MA in anthropology from University College London and has studied at the London Fine Art Studios and the Arts Students League of New York.

Authors

Amy Clare

Amy Clare is a PhD candidate in the STS Department at the Technical University of Munich. Her work explores genetically edited livestock in agriculture and experimental science. Her dissertation examines how aspects of livestock agriculture become reconfigured in relation to biotechnology, through the case of CRISPR-mediated xenotransplantation science.

Cite as

Clare, Amy. 2023. “The Boars of Biotech.” Anthropology News website, March 14, 2023.