Thomas R. O'Donnell

Iowa company produced first pig kidney grafted onto a human patient

In Industry Research, Uncategorized, University research on November 28, 2021 at 4:24 pm
A genetically engineered pig kidney, raised in Iowa, is cleaned and prepared for transplantation to a human. Credit: Joe Carrotta for NYU Langone Health.

The day is nearing when doctors will safely transplant animal kidneys, hearts and other organs to ailing humans.

When they do, there’s a good chance that animals providing those body parts will be grown in Iowa – at least in the early stages.

In September, New York University surgeons connected a kidney from a genetically modified pig to a patient destined to die but kept alive on a ventilator. (The subject’s family consented to the experiment.) The kidney functioned normally, removing urine and other wastes from the person’s bloodstream, for more than two days. Because researchers had modified the pig’s genetic code, there were no signs of immediate – hyperacute – rejection from the patient’s immune system.

The Associated Press reported last month that the pig was part of a herd of 100 raised “in tightly controlled conditions at a facility in Iowa.”

I’ve identified the Iowa company that did the work and the facility’s likely, approximate location. What’s less clear is what animal-sourced organs could mean for the state.

There’s no doubt that transplant-worthy organs are needed. As of this month, more than 90,000 Americans were on waiting lists for a donor kidney, the U.S. Department of Health and Human Services’ Organ Procurement and Transplantation Network reports. That includes more than 500 Iowans.

I won’t delve deeply into the technology of the transplant experiment and how scientists modified the pig involved. You can learn more at the AP story above, at this New York Times article (behind a paywall) and this press release from NYU Langone Health.

In effect, researchers with biotech company Revivicor – now a subsidiary of conglomerate United Therapeutics – used genetic engineering to knock out a pig gene that encodes for alpha-gal, a sugar the human body targets as foreign, generating an immediate immune response that rejects the organ.

Scientists then cloned the modified cells, probably by transferring their nuclei into pig egg cells or early embryos, replacing their existing genetic material – the blueprint for building a pig. Technicians implanted the resulting embryos into the uteri of surrogate sows, which gave birth to the cloned piglets.

Few Iowa companies do this kind of work. The first I thought of was Sioux Center’s Trans Ova Genetics, which clones livestock and preserves their cells for clients and provides similar services. Trans Ova implants embryos in its own surrogate animals, then oversees offspring’s births and raises them to weaning.

Richard Remillard, Trans Ova director of operations development, told me the company is, indeed, working with United Therapeutics/Revivicor through Exemplar Genetics, a subsidiary. Remillard referred me to company president David Faber, a veterinary medicine Ph.D. and a Trans Ova founder. I’ve not heard back since giving Remillard my number nor since leaving an additional message.

The surgical team at NYU Langone Health examines the porcine kidney for any signs of hyperacute rejection. It was implanted outside the body to allow for observation and tissue sampling during the 54-hour study period. Credit: Joe Carrotta for NYU Langone Health.

Trans Ova/Exemplar has an interesting history. Exemplar spun out from the University of Iowa, based on 2008 research to develop an animal model for cystic fibrosis (CF), a genetic condition that leads to thickened mucus in the lungs, affecting breathing and digestion. Scientists believed standard mouse models are inadequate for research; pig physiology more closely resembles that of humans.

Working with University of Missouri researchers, UI’s Michael Welsh and colleagues produced pigs genetically modified to develop CF symptoms. Welsh went on to cofound Exemplar. (Welsh, through a UI spokesperson, said he no longer has an advisory or financial interest in the company.) Exemplar, now called Precigen Exemplar (I’ll explain why shortly), has since gone on to develop miniature pigs modified for research into heart, kidney and blood conditions and into cancer.

Relevant to United Therapeutics/Revivicor: Exemplar also provides “animal husbandry services specifically designed for research animals,” including nutrition, health, housing and climate control, plus handling sanitation and more for these sensitive – and prized – customized critters.

Trans Ova apparently had a hand in Exemplar from the start; in 2009 it received a forgivable $1 million state loan to spin it out as a separate company, Genetic Engineering & Biotechnology News recounted in 2015. That was roughly a year after Intrexon, a synthetic biology company, bought Trans Ova – including Exemplar – for $110 million.

In January 2020, Intrexon changed its name to Precigen. Trans Ova’s website notes it is “Proudly Owned By Precigen.” Exemplar Genetics still lists a Sioux Center address.

It’s confusing, but to restate, here’s the lineage: Trans Ova owns Exemplar. Intrexon, now Precigen, bough Trans Ova, including Exemplar.

These organ-donor pigs probably are produced in or near Sioux County, but I don’t know the exact location and wouldn’t disclose it if I did, lest it become a target for animal rights extremists. Given that and other factors, it’s understandable that United Therapeutics spokesman Dewey Steadman declined to comment and I have yet to hear more from Trans Ova. Neither wants the headaches of added publicity. (To be fair, a Trans Ova receptionist told me that Faber is heavily booked and unlikely to reply soon.)

The porcine kidney appears healthy and the ureter is prepared to allow for urine production. Credit: Joe Carrotta for NYU Langone Health.

Pigs can grow anywhere, so Iowa State University swine experts I talked with guessed that United Therapeutics, based in Maryland, and Revivicor, based in Virginia, chose Iowa to capitalize on expertise here. They were right.

Christopher Tuggle, an animal science professor specializing in swine genetics, told me he spoke a few years ago with John Swart, then Exemplar’s president. Tuggle and colleagues have developed a line of severe combined immunodeficient (SCID) pigs – ones with nonfunctioning or impaired immune systems – and are studying them as potential research models for human disease. Swart conferred with him because Exemplar was considering producing SCID pigs, Tuggle said.

Because they have no immune system, even a common cold could kill SCID pigs. Tuggle’s group keeps them in pristine, isolated bioBUBBLES, equipped with HEPA (high-efficiency particulate air) filters that capture bacteria and viruses, positive pressure so air doesn’t enter when the door is opened, and meticulous sanitation.

United Therapeutics/Revivicor’s GalSafe pigs, as the company has trademarked them, wouldn’t need a facility with that extreme level of biosafety, Tuggle said, but they would require tight conditions. Especially since pigs and humans share many diseases, “you want to be sure … you’re not introducing any disease into the human,” particularly viral illnesses, via transplanted organs. That means “producing the pig in basically medical practices so the tissues you harvest from them would be completely free of any potential threat to the patient.”

Such measures also protect the company’s investment from an outside disease that could decimate the herd.

Tuggle said he last had contact with the company before the pandemic.

No one will receive a pig kidney transplant tomorrow, next month or even next year. Arduous experiments, clinical tests and regulatory approvals lie ahead. “This was a good first step but only a relatively small step,” Tuggle said, noting “this only solves the hyperacute rejection” and not other biological issues that can lead to organ rejection. Medical researchers also must address porcine endogenous retroviruses, viral DNA embedded in the pig genome that could cause human disease via transplant.

United Therapeutics/Revivicor and other companies probably will surmount those obstacles, leading to an industry in engineered organs. The ISU experts diverge in how that will affect Iowa and its economy.

Max Rothschild, a recently retired animal science professor specializing in swine breeding and genetics, sees little impact. Transplant patients would benefit, but no “farmer raising pigs in a 5,000 grower-finisher unit is going to drop everything to raise this kind of pig. That’s not going to happen.” Instead, some elite farmers or breeding companies could produce hogs for transplant under specific ethical or medical standards.

Jason Ross, Lloyd Anderson Endowed Professor in Physiology and director of the Iowa Pork Industry Center, is more optimistic. Organ-producing companies may Iowa’s concentration of swine production infrastructure and veterinary medicine expertise attractive, he says, and the state’s central location is an advantage. “Delivering that product, those pigs that can serve as organ donors, we would be in a position to do that all over the country as a centralized hub.”

Tuggle says the attention Iowa receives from raising animals for transplant organs could burnish the state’s biotechnology reputation. Besides his research, Ross also experiments with pig genome modifications to make the animals more useful as models for human disease, from immune problems to cancer – work similar to Exemplar’s main mission. Some projects also could cross into food production, with modifications targeting food allergies or fat content – if consumers can overcome objections to eating genetically modified meat.

I suspect few Iowans will have a problem with that – but what about manufacturing animals to provide spare parts for humans? In the next post, I’ll examine the ethics of the situation.

  1. You should send this to Franken.

    On Sun, Nov 28, 2021 at 4:24 PM Iowa Science Interface wrote:

    > iowascienceinterface posted: ” A genetically engineered pig kidney, raised > in Iowa, is cleaned and prepared for transplantation to a human. Credit: > Joe Carrotta for NYU Langone Health. The day is nearing when doctors will > safely transplant animal kidneys, hearts and other organs to” >

  2. […] – replacing human organs with ones from animals – has advanced since I reported last fall that the first pig kidney attached to a living human came from […]

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